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Cerebellar hemorrhage as an atypical complication of meningococcal meningitis

2008; Elsevier BV; Volume: 12; Issue: 5 Linguagem: Inglês

10.1016/j.ijid.2008.01.007

1878-3511

Alexandre Leite de Souza, Jaques Sztajnbok, Antônio Carlos Seguro,

Influenza Virus Research Studies

Cerebrovascular phenomena have been well documented in traditional reviews of bacterial meningitis in children and adults alike.1Weisfelt M. de Gans J. van der Poll T. van de Beek D. Pneumococcal meningitis in adults: new approaches to management and prevention.Lancet Neurol. 2006; 5: 332-342Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar, 2van de Beek D. de Gans J. Tunkel A.R. Wijdicks E.F. Community-acquired bacterial meningitis in adults.N Engl J Med. 2006; 354: 44-53Crossref PubMed Scopus (630) Google Scholar, 3Swartz M.N. Bacterial meningitis: more involved than just the meninges.N Engl J Med. 1984; 311: 912-914Crossref PubMed Scopus (79) Google Scholar, 4Pfister H.W. Borasio G.D. Dirnagl U. Bauer M. Einhaupl K.M. Cerebrovascular complications of bacterial meningitis in adults.Neurology. 1992; 42: 1497-1504Crossref PubMed Google Scholar, 5Gironell A. Domingo P. Mancebo J. Coll P. Marti-Vilalta J.L. Hemorrhagic stroke as a complication of bacterial meningitis in adults: report of three cases and review.Clin Infect Dis. 1995; 21: 1488-1491Crossref PubMed Scopus (18) Google Scholar, 6Hardman J.M. Earle K.M. Meningococcal infections: a review of 200 fatal cases.J Neuropathol Exp Neurol. 1967; 26: 119PubMed Google Scholar However, this is the first documented case of cerebellar hemorrhage linked to Neisseria meningitidis serogroup B in a child. A previously healthy 5-year-old boy presented with a 36-h history of muscle tenderness, fever, and headache. In the preceding 3 h, the patient had developed petechiae on his skin and mucosal surfaces. Upon examination, he presented neck stiffness, and his Glasgow Coma Scale score was 14. His vital signs were as follows: axillary temperature 37.5 °C, pulse 150 bpm, respiration 30 breaths/min, and blood pressure 100/60 mmHg. The preliminary diagnosis was meningococcal meningitis with sepsis. Therefore, we initiated antibiotic treatment with intravenous ceftriaxone (100 mg/kg/day for seven days) and dexamethasone (0.6 mg/kg/day for four days). His white blood cell (WBC) count was 18.5 × 109/l and platelet count was 52 × 109 cells/l. Coagulation studies demonstrated an international normalized ratio (INR) of 2.0 and an activated partial thromboplastin time of 60 s. A computed tomography (CT) scan of the brain was normal, and a lumbar puncture was performed after transfusion of fresh-frozen plasma and platelets. The cerebrospinal fluid (CSF) contained 940 × 106 WBC/l and 269 mg/dl of protein, and the CSF glucose/blood glucose ratio was 0.10. Gram stain of the CSF showed Gram-negative diplococci. The results of the latex agglutination test and counterimmunoelectrophoresis of the CSF were positive for N. meningitidis serogroup B, as were those of the CSF culture. The patient demonstrated clinical and hemostatic improvement during the first 24 h. However, on the second day of hospitalization, his level of consciousness deteriorated rapidly. A second CT scan of the brain revealed a high-density area in the right cerebellar hemisphere, suggesting cerebellar hemorrhage (Figure 1). The platelet count was 82 × 109 cells/l and coagulation studies demonstrated an INR of 1.6. Transesophageal echocardiogram and extracranial carotid Doppler study results were within normal limits. One week after the hemorrhagic phenomenon, a neurological examination showed a nearly complete clinical recovery and a CT scan revealed virtually total absorption of the hematoma (Figure 2). In a routine follow-up examination, performed 9 months later, the patient reported no further problems.Figure 2Brain CT image on the seventh day of hospitalization, showing a virtually total absorption of the hematoma.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Cerebrovascular accidents are determinants of unfavorable outcomes in bacterial meningitis, and they manifest clinically as focal neurological deficits or as a decrease in consciousness.2van de Beek D. de Gans J. Tunkel A.R. Wijdicks E.F. Community-acquired bacterial meningitis in adults.N Engl J Med. 2006; 354: 44-53Crossref PubMed Scopus (630) Google Scholar, 4Pfister H.W. Borasio G.D. Dirnagl U. Bauer M. Einhaupl K.M. Cerebrovascular complications of bacterial meningitis in adults.Neurology. 1992; 42: 1497-1504Crossref PubMed Google Scholar, 5Gironell A. Domingo P. Mancebo J. Coll P. Marti-Vilalta J.L. Hemorrhagic stroke as a complication of bacterial meningitis in adults: report of three cases and review.Clin Infect Dis. 1995; 21: 1488-1491Crossref PubMed Scopus (18) Google Scholar The impairment of cerebral vessels during meningitis has been demonstrated in histopathological studies in which arteritis, thrombophlebitis, and cerebral infarcts were detected,4Pfister H.W. Borasio G.D. Dirnagl U. Bauer M. Einhaupl K.M. Cerebrovascular complications of bacterial meningitis in adults.Neurology. 1992; 42: 1497-1504Crossref PubMed Google Scholar, 6Hardman J.M. Earle K.M. Meningococcal infections: a review of 200 fatal cases.J Neuropathol Exp Neurol. 1967; 26: 119PubMed Google Scholar as well as in reports of angiographic changes of cerebral arteries, including vessel wall irregularities, vasospasm, and focal dilatation.1Weisfelt M. de Gans J. van der Poll T. van de Beek D. Pneumococcal meningitis in adults: new approaches to management and prevention.Lancet Neurol. 2006; 5: 332-342Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar, 4Pfister H.W. Borasio G.D. Dirnagl U. Bauer M. Einhaupl K.M. Cerebrovascular complications of bacterial meningitis in adults.Neurology. 1992; 42: 1497-1504Crossref PubMed Google Scholar In a prospective study of 86 adults with bacterial meningitis, it was reported that 13 (37.1%) developed cerebrovascular complications.4Pfister H.W. Borasio G.D. Dirnagl U. Bauer M. Einhaupl K.M. Cerebrovascular complications of bacterial meningitis in adults.Neurology. 1992; 42: 1497-1504Crossref PubMed Google Scholar However, the authors isolated N. meningitidis in only one of the patients presenting a cerebrovascular accident. In patients with meningitis caused by N. meningitidis, mortality rates range from 3 to 13%, and morbidity rates range from 3 to 7%.2van de Beek D. de Gans J. Tunkel A.R. Wijdicks E.F. Community-acquired bacterial meningitis in adults.N Engl J Med. 2006; 354: 44-53Crossref PubMed Scopus (630) Google Scholar Although stroke caused by N. meningitidis affects adults5Gironell A. Domingo P. Mancebo J. Coll P. Marti-Vilalta J.L. Hemorrhagic stroke as a complication of bacterial meningitis in adults: report of three cases and review.Clin Infect Dis. 1995; 21: 1488-1491Crossref PubMed Scopus (18) Google Scholar, 7Hsu S.S. Kim H.S. Meningococcal meningitis presenting as stroke in an afebrile adult.Ann Emerg Med. 1998; 32: 620-623Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar, 8de Souza A.L. de Oliveira A.C. Romano C.C. Sztajnbok J. Duarte A.J. Seguro A.C. Interleukin-6 activation in ischemic stroke caused by Neisseria meningitidis serogroup C.Int J Cardiol. 2008; 127: e160-e163Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar and children9Mankhambo L.A. Makwana N.V. Carrol E.D. Beare N.A. Taylor T. Kampondeni S. et al.Persistent visual loss as a complication of meningococcal meningitis.Pediatr Infect Dis J. 2006; 25: 566-567Crossref PubMed Scopus (7) Google Scholar alike, it is an atypical event6Hardman J.M. Earle K.M. Meningococcal infections: a review of 200 fatal cases.J Neuropathol Exp Neurol. 1967; 26: 119PubMed Google Scholar and has been linked to serogroups B,5Gironell A. Domingo P. Mancebo J. Coll P. Marti-Vilalta J.L. Hemorrhagic stroke as a complication of bacterial meningitis in adults: report of three cases and review.Clin Infect Dis. 1995; 21: 1488-1491Crossref PubMed Scopus (18) Google Scholar, 9Mankhambo L.A. Makwana N.V. Carrol E.D. Beare N.A. Taylor T. Kampondeni S. et al.Persistent visual loss as a complication of meningococcal meningitis.Pediatr Infect Dis J. 2006; 25: 566-567Crossref PubMed Scopus (7) Google Scholar C,8de Souza A.L. de Oliveira A.C. Romano C.C. Sztajnbok J. Duarte A.J. Seguro A.C. Interleukin-6 activation in ischemic stroke caused by Neisseria meningitidis serogroup C.Int J Cardiol. 2008; 127: e160-e163Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar and Y.7Hsu S.S. Kim H.S. Meningococcal meningitis presenting as stroke in an afebrile adult.Ann Emerg Med. 1998; 32: 620-623Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar A complex web of cells and molecules has been implicated in meningococcal infection.10Hermans P.W. Hibberd M.L. Booy R. Daramola O. Hazelzet J.A. de Groot R. et al.4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease.Lancet. 1999; 354: 556-560Abstract Full Text Full Text PDF PubMed Scopus (287) Google Scholar, 11Weisfelt M. Determann R.M. de Gans J. van der Ende A. Levi M. van de Beek D. et al.Procoagulant and fibrinolytic activity in cerebrospinal fluid from adults with bacterial meningitis.J Infect. 2007; 54: 545-550Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar However, the pathogenesis of stroke in a patient with meningococcal meningitis has not been fully deciphered. It is believed to be a phenomenon with multiple molecular/cellular mechanisms and pathogenic pathways.2van de Beek D. de Gans J. Tunkel A.R. Wijdicks E.F. Community-acquired bacterial meningitis in adults.N Engl J Med. 2006; 354: 44-53Crossref PubMed Scopus (630) Google Scholar, 4Pfister H.W. Borasio G.D. Dirnagl U. Bauer M. Einhaupl K.M. Cerebrovascular complications of bacterial meningitis in adults.Neurology. 1992; 42: 1497-1504Crossref PubMed Google Scholar, 5Gironell A. Domingo P. Mancebo J. Coll P. Marti-Vilalta J.L. Hemorrhagic stroke as a complication of bacterial meningitis in adults: report of three cases and review.Clin Infect Dis. 1995; 21: 1488-1491Crossref PubMed Scopus (18) Google Scholar, 8de Souza A.L. de Oliveira A.C. Romano C.C. Sztajnbok J. Duarte A.J. Seguro A.C. Interleukin-6 activation in ischemic stroke caused by Neisseria meningitidis serogroup C.Int J Cardiol. 2008; 127: e160-e163Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 11Weisfelt M. Determann R.M. de Gans J. van der Ende A. Levi M. van de Beek D. et al.Procoagulant and fibrinolytic activity in cerebrospinal fluid from adults with bacterial meningitis.J Infect. 2007; 54: 545-550Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Cytokines play a pivotal role in the genesis of endothelial dysfunction and imbalance of hemostatic forces,10Hermans P.W. Hibberd M.L. Booy R. Daramola O. Hazelzet J.A. de Groot R. et al.4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease.Lancet. 1999; 354: 556-560Abstract Full Text Full Text PDF PubMed Scopus (287) Google Scholar, 11Weisfelt M. Determann R.M. de Gans J. van der Ende A. Levi M. van de Beek D. et al.Procoagulant and fibrinolytic activity in cerebrospinal fluid from adults with bacterial meningitis.J Infect. 2007; 54: 545-550Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar as reflected by coagulopathy, low platelet counts, and hemorrhagic skin lesions in our patient. Interestingly, we have reported a phenomenon of cytokine expression within the central nervous system of a patient with meningococcal infection complicated by ischemic stroke.8de Souza A.L. de Oliveira A.C. Romano C.C. Sztajnbok J. Duarte A.J. Seguro A.C. Interleukin-6 activation in ischemic stroke caused by Neisseria meningitidis serogroup C.Int J Cardiol. 2008; 127: e160-e163Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Concentrations of interleukin-6 were notably elevated in the cerebrospinal fluid of the patient.8de Souza A.L. de Oliveira A.C. Romano C.C. Sztajnbok J. Duarte A.J. Seguro A.C. Interleukin-6 activation in ischemic stroke caused by Neisseria meningitidis serogroup C.Int J Cardiol. 2008; 127: e160-e163Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Recently, reactive oxygen species and reactive nitrogen intermediates have also been identified as critical mediators of the pathogenesis of bacterial meningitis.1Weisfelt M. de Gans J. van der Poll T. van de Beek D. Pneumococcal meningitis in adults: new approaches to management and prevention.Lancet Neurol. 2006; 5: 332-342Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar While cytokines and other mediators involved in the genesis of endothelial dysfunction and coagulopathy are released by several cell types within the central nervous system and vascular tree,1Weisfelt M. de Gans J. van der Poll T. van de Beek D. Pneumococcal meningitis in adults: new approaches to management and prevention.Lancet Neurol. 2006; 5: 332-342Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar, 2van de Beek D. de Gans J. Tunkel A.R. Wijdicks E.F. Community-acquired bacterial meningitis in adults.N Engl J Med. 2006; 354: 44-53Crossref PubMed Scopus (630) Google Scholar, 4Pfister H.W. Borasio G.D. Dirnagl U. Bauer M. Einhaupl K.M. Cerebrovascular complications of bacterial meningitis in adults.Neurology. 1992; 42: 1497-1504Crossref PubMed Google Scholar, 5Gironell A. Domingo P. Mancebo J. Coll P. Marti-Vilalta J.L. Hemorrhagic stroke as a complication of bacterial meningitis in adults: report of three cases and review.Clin Infect Dis. 1995; 21: 1488-1491Crossref PubMed Scopus (18) Google Scholar, 8de Souza A.L. de Oliveira A.C. Romano C.C. Sztajnbok J. Duarte A.J. Seguro A.C. Interleukin-6 activation in ischemic stroke caused by Neisseria meningitidis serogroup C.Int J Cardiol. 2008; 127: e160-e163Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 10Hermans P.W. Hibberd M.L. Booy R. Daramola O. Hazelzet J.A. de Groot R. et al.4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease.Lancet. 1999; 354: 556-560Abstract Full Text Full Text PDF PubMed Scopus (287) Google Scholar, 11Weisfelt M. Determann R.M. de Gans J. van der Ende A. Levi M. van de Beek D. et al.Procoagulant and fibrinolytic activity in cerebrospinal fluid from adults with bacterial meningitis.J Infect. 2007; 54: 545-550Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar widespread endothelial breakdown can continue, even if the CSF has been sterilized through antibiotic therapy. Therefore, it is probable that, in meningococcal infection, strokes are related to both local (endothelial damage) as well as systemic (imbalance of hemostatic forces) mechanisms. Conflict of interest: No conflict of interest to declare.