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Neurologic Complications of Infective Endocarditis: A Joint Model for a Septic Thromboembolism and Inflammatory Small Vessel Disease

Cantier, Marie MD1,2; Sabben, Candice MD1,3; Adle-Biassette, Homa MD, PhD4; Louedec, Liliane1; Delbosc, Sandrine PhD1; Desilles, Jean-Philippe MD, PhD1,5; Journé, Clément1,6; Diallo, Devy PhD1; Ou, Phalla MD, PhD1,6,7; Klein, Isabelle MD, PhD8; Chau, Françoise MD9; Lefort, Agnès MD, PhD9,10; Iung, Bernard MD, PhD11; Duval, Xavier MD, PhD12; Olivot, Jean-Marc MD, PhD13; Ho-Tin-Noe, Benoit PhD1; Michel, Jean-Baptiste MD, PhD1; Sonneville, Romain MD, PhD1,14; Mazighi, Mikael MD, PhD1,15,16

doi: 10.1097/CCM.0000000000003796
Online Laboratory Investigations
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Objectives: Embolic events from vegetations are commonly accepted as the main mechanism involved in neurologic complications of infective endocarditis. The pathophysiology may imply other phenomena, including vasculitis. We aimed to define the cerebral lesion spectrum in an infective endocarditis rat model.

Design: Experimental model of Staphylococcus aureus or Enterococcus faecalis infective endocarditis. Neurologic lesions observed in the infective endocarditis model were compared with three other conditions, namely bacteremia, nonbacterial thrombotic endocarditis, and healthy controls.

Setting: Research laboratory of a university hospital.

Subjects: Male Wistar rats.

Interventions: Brain MRI, neuropathology, immunohistochemistry for astrocyte and microglia, and bacterial studies on brain tissue were used to characterize neurologic lesions.

Measurements and Main Results: In the infective endocarditis group, MRI revealed at least one cerebral lesion in 12 of 23 rats (52%), including brain infarctions (n = 9/23, 39%) and cerebral microbleeds (n = 8/23, 35%). In the infective endocarditis group, neuropathology revealed brain infarctions (n = 12/23, 52%), microhemorrhages (n = 10/23, 44%), and inflammatory processes (i.e., cell infiltrates including abscesses, vasculitis, meningoencephalitis, and/or ependymitis; n = 11/23, 48%). In the bacteremia group, MRI studies were normal and neuropathology revealed only hemorrhages (n = 2/11, 18%). Neuropathologic patterns observed in the nonbacterial thrombotic endocarditis group were similar to those observed in the infective endocarditis group. Immunochemistry revealed higher microglial activation in the infective endocarditis group (n = 11/23, 48%), when compared with the bacteremia (n = 1/11, 9%; p = 0.03) and nonbacterial thrombotic endocarditis groups (n = 0/7, 0%; p = 0.02).

Conclusions: This original model of infective endocarditis recapitulates the neurologic lesion spectrum observed in humans and suggests synergistic mechanisms involved, including thromboembolism and cerebral vasculitis, promoted by a systemic bacteremia-mediated inflammation.

1Inserm U1148, Laboratory for Vascular Translational Science (LVTS), Bichat Hospital, Paris University, Sorbonne Paris Cité, Paris, France.

2Department of Neurology, Saint-Antoine Hospital, AH-HP, Paris University, Sorbonne Universités, Paris, France.

3Department of Neurology, Fondation Rothschild, Paris, France.

4Department of Pathology, Lariboisière Hospital, AP-HP, Paris University, Sorbonne Paris Cité, Paris, France.

5Department of Interventional Neuroradiology, Fondation Rothschild, Paris, France.

6Fédération de Recherche en Imagerie Multimodale (FRIM), Paris University, Sorbonne Paris Cité, Paris, France.

7Department of Radiology, Bichat Hospital, AP-HP, Paris University, Sorbonne Paris Cité, Paris, France.

8Department of Radiology, Clinique Labrouste, Paris, France.

9Inserm U1137, Infection Antimicrobials Modelling Evolution (IAME), Bichat Hospital, Paris University, Sorbonne Paris Cité, Paris, France.

10Internal Medicine Department, Beaujon Hospital, Clichy, AP-HP, Paris University, Sorbonne Paris Cité, Paris, France.

11Department of Cardiology, Bichat Hospital, AP-HP, Paris University, Sorbonne Paris Cité, Paris, France.

12Inserm CIC 1425, Bichat Hospital, AP-HP, IAME UMR 1138, Paris University, Sorbonne Paris Cité, Paris, France.

13Department of Neurology, Purpan Hospital, Toulouse, France.

14Department of Intensive Care Medicine and Infectious Diseases, Bichat Hospital, AP-HP, Paris University, Sorbonne Paris Cité, Paris, France.

15Department of Neurology and Stroke Centre, Lariboisière Hospital, AP-HP, Paris University, Sorbonne Paris Cité, Paris, France.

16Département Hospitalo-Universistaire Neurovasc, Paris, France.

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Supported, in part, by the Société Française NeuroVasculaire.

Dr. Cantier received support for article research from Société Française de Neurologie Vasculaire. Dr. Olivot received funding from consulting for Servier, Medtronic, and Astra Zeneca, and he received speaker fees from Bristol Myers Squibb and Pfizer. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: marie.cantier@aphp.fr; mikael.mazighi@aphp.fr

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