Bacterial Infections of the Central Nervous System PDF
Preview Bacterial Infections of the Central Nervous System
HANDBOOK OF CLINICAL NEUROLOGY Series Editors MICHAEL J. AMINOFF, FRANC¸OIS BOLLER, AND DICK F. SWAAB VOLUME 96 EDINBURGH LONDON NEW YORK OXFORD PHILADELPHIA ST LOUIS SYDNEY TORONTO 2010 ELSEVIERB.V Radarweg29,1043NX,Amsterdam,TheNetherlands #2010,ElsevierB.V.Allrightsreserved. Nopartofthispublicationmaybereproducedortransmittedinanyformorbyanymeans,electronicor mechanical,includingphotocopying,recording,oranyinformationstorageandretrievalsystem,without permissioninwritingfromthepublisher.PermissionsmaybesoughtdirectlyfromElsevier’sRights Department:phone:(þ1)2152393804(US)or(þ44)1865843830(UK);fax:(þ44)1865853333; e-mail:healthpermissions@elsevier.com.Youmayalsocompleteyourrequeston-lineviatheElsevierwebsite athttp://www.elsevier.com/permissions. ISBN:9780444520159 BritishLibraryCataloguinginPublicationData AcataloguerecordforthisbookisavailablefromtheBritishLibrary LibraryofCongressCataloginginPublicationData AcatalogrecordforthisbookisavailablefromtheLibraryofCongress Notice Knowledgeandbestpracticeinthisfieldareconstantlychanging.Asnewresearchandexperiencebroadenour knowledge,changesinpractice,treatmentanddrugtherapymaybecomenecessaryorappropriate.Readersare advisedtocheckthemostcurrentinformationprovided(i)onproceduresfeaturedor(ii)bythemanufacturerof eachproducttobeadministered,toverifytherecommendeddoseorformula,themethodanddurationof administration,andcontraindications.Itistheresponsibilityofthepractitioner,relyingontheirownexperience andknowledgeofthepatient,tomakediagnoses,todeterminedosagesandthebesttreatmentforeachindividual patient,andtotakeallappropriatesafetyprecautions.Tothefullestextentofthelaw,neitherthePublishernorthe Editorsassumesanyliabilityforanyinjuryand/ordamagetopersonsorpropertyarisingoutorrelatedtoanyuse ofthematerialcontainedinthisbook. ThePublisher PrintedinChina The CommissioningEditor:TimothyHorne Publisher's policy is to use DevelopmentEditor:MichaelParkinson paper manufactured ProjectManager:AnithaRajarathnam from sustainable forests Designer:KirsteenWright Handbook of Clinical Neurology 3rd series Available titles Vol. 79, The human hypothalamus: basic and clinical aspects, Part I, D.F. Swaab ISBN 0444513574 Vol. 80, The human hypothalamus: basic and clinical aspects, Part II, D.F. Swaab ISBN 0444514902 Vol. 81, Pain, F. Cervero and T.S. Jensen, eds. ISBN 0444519017 Vol. 82, Motor neurone disorders and related diseases, A.A. Eisen and P.J. Shaw, eds. ISBN 0444518940 Vol.83,Parkinson’sdiseaseandrelateddisorders,PartI,W.C.KollerandE.Melamed,eds.ISBN9780444519009 Vol.84,Parkinson’sdiseaseandrelateddisorders,PartII,W.C.KollerandE.Melamed,eds.ISBN9780444528933 Vol. 85, HIV/AIDS and the nervous system, P. Portegies and J. Berger, eds. ISBN 9780444520104 Vol. 86, Myopathies, F.L. Mastaglia and D. Hilton Jones, eds. ISBN 9780444518966 Vol. 87, Malformations of the nervous system, H.B. Sarnat and P. Curatolo, eds. ISBN 9780444518965 Vol.88,Neuropsychologyandbehaviouralneurology,G.GoldenbergandB.C.Miller,eds.ISBN9780444518972 Vol. 89, Dementias, C. Duyckaerts and I. Litvan, eds. ISBN 9780444518989 Vol. 90, Disorders of Consciousness, G.B. Young and E.F.M. Wijdicks, eds. ISBN 9780444518958 Vol. 91, Neuromuscular Junction Disorders, A.G. Engel, ed. ISBN 9780444520081 Vol. 92, Stroke – Part I: Basic and epidemiological aspects, M. Fisher, ed. ISBN 9780444520036 Vol. 93, Stroke – Part II: Clinical manifestations and pathogenesis, M. Fisher, ed. ISBN 9780444520043 Vol. 94, Stroke – Part III: Investigations and management, M. Fisher, ed. ISBN 9780444520050 Vol. 95, History of neurology, S. Finger, F. Boller and K.L. Tyler, eds. ISBN 9780444520098 Forthcoming titles Headache, G. Nappi and M.A. Moskowitz, eds. ISBN 9780444521392 Sleep Disorders – Part I, P. Montagna and S. Chokroverty, eds. ISBN 9780444520067 Sleep Disorders – Part II, P. Montagna and S. Chokroverty, eds. ISBN 9780444520074 Ataxic Disorders, S.H. Subramony and A. Durr, eds. ISBN 9780444518927 Foreword The recent development of new vaccines and antibiotics generated the hope that infectious diseases, particularly those affecting the nervous system, would become much less common than in the past. Unfortunately, this hope hasnotbeenrealizedforavarietyofreasons.Vaccinationsandtheuseofantibioticsrequireacertaindegreeofmed- icalsophisticationandtendtobeexpensive.Moreover,maintaininganadequatelevelofhygieneisoftendifficultin overcrowdedareas.Thesefactorsexplaininpartwhytheprevalenceofinfectionsisparticularlymarkedamongless affluentpopulations.Inaddition, there is increasingoppositiontovaccination incertainsegmentsofthe population of developed countries. Another key factor is the immunosuppression that accompanies infections with human immunodeficiencyvirus(HIV)andfollowsorgantransplantations,resultinginamarkedresurgenceofdiseasessuch as tuberculosis and syphilis, previously considered to be successfully contained. Finally, climate changes and increasing mobility of populations may also contribute to the continuing spread of infectious diseases. The first series of the Handbook included three volumes published in 1978. They covered bacterial agents (volume 33), viruses (volume 34), and parasitic diseases (volume 35). At the time, HIV infection and acquired immunodeficiency syndrome (AIDS) had not yet been recognized as a problem of epidemic proportion. In the second series, one volume was dedicated to microbial diseases and another to viral infections including AIDS. The very considerable development of the field is reflected by the several volumes dealing with infection in this series.HIV/AIDSwasthesubjectofoneofthefirstvolumesofthenewseries(volume85).Wearenowpleasedto present a volume dedicated to bacterial infections of the central nervous system. Neurovirology, parasitology, fungal infections, and tropical neurology will be covered in future volumes. Thenewvolumecoversadvancesinthefieldofbacterialinfectionsandincludesanumberofnewtopics.Itpro- vides insight into the pathophysiological mechanism of bacterial CNS infections and covers the main principles of modern antimicrobial therapy as well as the bases for new therapeutic strategies for bacterial infections. There is considerable emphasis on new diagnostic techniques, particularly imaging and new laboratory tests. The volume was edited by Karen L. Roos and Allan R. Tunkel. As series editors, we reviewed all the chapters in the volume and madesuggestions for improvement, but weare delightedthatthe volumeeditors and chapter authors produced such scholarly and comprehensive accounts of different aspects of bacterial infections. Hence we hope that the volume will appeal to clinicians and neuroscientists alike. Significant new advances continue to occur, leading to new insights that demand a critical appraisal. Our goal is to provide basic researchers with the foundations for newinvestigations.Wealsohopethatclinicianswillgainfromthisvolumeathoroughunderstandingoftheclinical features and management of the many neurological manifestations of bacterial infections. In addition to the print form,theHandbookserieswillsoonbeavailableelectronicallyonElsevier’sScienceDirectsite.Thisshouldmake it more accessible to readers and should also facilitate searches for specific information. Wewishtoexpressourdeepgratitudetothetwovolumeeditorsandtothenumerousauthorswhocontributed theirtimeandexpertisetosummarizedevelopmentsintheirfieldandhelpedputtogetherthisoutstandingvolume. As always, we are also grateful to the team at Elsevier – and in particular to Mr. Michael Parkinson and Mr. TimothyHorneinEdinburgh–fortheirunfailingandexpertassistanceinthedevelopmentandproductionofthis volume. Michael J. Aminoff Franc¸ois Boller Dick F. Swaab Preface Bacterialinfectionsofthecentral nervoussystem(CNS)areoftenchallengingintermsofestablishingtheetiolo- gic diagnosis,initiatingantimicrobial therapy, andmanaging complications. Many ofthese infectionscontinue to be important causes of morbidity and mortality, such that a rapid approach to management is critically important to increase the likelihood of a good neurological outcome. Furthermore, the increased numbers of immunocom- promised patients (e.g., following transplantation or infection with human immunodeficiency virus) have further complicated diagnosis and management. RecentdecadeshavewitnessedprofoundadvancesintheapproachtothepatientwithbacterialCNSinfections. Advances in neuroimaging techniques, such as computed tomography and magnetic resonance imaging, have greatlyimprovedtheabilitytodiagnoseCNSstructurallesionsandmonitortheirresponsetotherapy.Nucleicacid amplificationtests,suchaspolymerasechainreaction(PCR),haveaidedintheidentificationofinfectiousagents thatarenotroutinelyisolatedusingconventionalculturetechniques.Withtheemergenceofbacterialstrainsresis- tanttostandardantimicrobialagents,thereisaneedforneweragentsthateffectivelycrosstheblood–brainbarrier anderadicatetheinfectingpathogen.Adjunctivetherapy,specificallywithdexamethasone,hasimprovedmorbid- ityandmortalityinpatientswithbacterialmeningitisandisnowpartofstandardpracticeguidelinesfortheman- agement of this important infection. Furthermore, the successful approach to bacterial CNS infections is multidisciplinary and often includes neurologists, neurosurgeons, and specialists in infectious diseases. Thisvolumeincludesfourchaptersthatelucidatethegeneralapproachtothepatientwithasuspectedbacterial CNSinfection.Thetopicscoveredincludethecharacteristic neuroimagingappearanceofspecificbacterial infec- tions and the limitations of neuroimaging; cerebrospinal fluid analysis with an emphasis on the use of newer diagnostic tests; the pathogenesis and pathophysiology of bacterial CNS infections, an understanding of which may lead to the development of other specific adjunctive strategies; and the principles of antimicrobial therapy. Other chapters review specific disease entities, including meningitis, focal CNS infections (e.g., brain abscess, subdural empyema, and epidural abscess), the neurological complications of endocarditis, suppurative venous sinus thrombosis, infections in the neurosurgical patient, and CNS diseases caused by selected infectious agents and toxins. The contributors are recognized experts in their fields, and have extensive clinical and investigative interests.Ourgoalwastocreateacomprehensivetreatisetobeusedbyphysicianswhocareforpatientswithbac- terial infections of the CNS. Karen L. Roos Allan R. Tunkel List of contributors A.J. Aksamit J.E. Greenlee Department of Neurology, Mayo Clinic College of DepartmentofNeurology,GeorgeE.WahlenVeterans Medicine, Rochester, MN, USA Affairs Medical Center; University of Utah School of Medicine, Salt Lake City, UT, USA R.E. Bartt Department of Neurological Sciences, Cook County R. Hasbun HospitalandRushMedicalCollege,Chicago,IL,USA DepartmentofMedicine,SectionofInfectiousDiseases, UniversityofTexasMedicalSchool,Houston,TX,USA T.P. Bleck Departments of Neurological Sciences, Neurosurgery, Medicine,andAnesthesiology,RushMedicalCollege; A.T. Karagulle-Kendi Rush University Medical Center, Chicago, IL, USA Department of Radiology, University of Minnesota School of Medicine, Minneapolis, MN, USA K.C. Bloch Department of Medicine (Infectious Diseases) and N. King Preventive Medicine, Division of Infectious Diseases, Department of Clinical Neurology, Indiana University Vanderbilt University Medical Center, Nashville, TN, School of Medicine, Indianapolis, IN, USA USA S.L. Leib D. Cadavid Department of Infectious Diseases, Institute for Center for Immunology and Inflammatory Diseases, Infectious Diseases, University of Bern, Bern, Division of Rheumatology, Allergy, & Immunology, Switzerland Massachusetts General Hospital, Charlestown, MA, USA P. Reddy L. Christie Department of Medicine, Division of Infectious Department of Pediatrics, Kaiser Oakland Medical Diseases, Northwestern Feinberg School of Medicine, CenterandChildren’sHospitalandResearchCenterat Chicago, IL, USA Oakland, Oakland, CA, USA K.L. Roos R.O. Darouiche Departments of Neurology and Neurosurgery, Indiana Infectious Disease Section and Center for Prostheses University School of Medicine, Indiana University Infection, Michael E. Debakey Veterans Affairs Hospital, Indianapolis, IN, USA Medical Center and Baylor College of Medicine, Houston, TX, USA W.M. Scheld C. Glaser Division of Infectious Diseases and International Viral and Rickettsial Disease Laboratory, Richmond, Health, University of Virginia, Charlottesville, VA, VA, USA USA xii LIST OF CONTRIBUTORS J. Sellner C. Truwit Department of Neurology, Technische Universita¨t Department of Radiology, Hennepin County Medical Mu¨nchen, Mu¨nchen, Germany Center, University of Minnesota School of Medicine, Minneapolis, MN, USA C. Sila Stroke & Cerebrovascular Center, Neurological A.R. Tunkel Institute, University Hospitals-Case Medical Center, Department of Medicine, Monmouth Medical Center, Case Western Reserve UniversitySchoolofMedicine, Long Branch, NJ, USA Cleveland, OH, USA D. van de Beek J.R. Starke Center of Infection and Immunity; Academic Medical DepartmentofPediatrics,BaylorCollegeofMedicine, Center, Amsterdam, The Netherlands Clinical Care Center, Texas Children’s Hospital, Houston, TX, USA H. Welch Department of Internal Medicine, Tulane University M.G. Ta¨uber School of Medicine, New Orleans, LA, Department of Infectious Diseases, Universita¨tsklinik USA fu¨r Infektiologie, University Hospital Inselspital Bern; Institute for Infectious Diseases, University of Bern, Bern, Switzerland J.R. Zunt Departments of Neurology, Global Health, J.M. Tessier Epidemiology and Medicine (Infectious Diseases), Division of Infectious Diseases, Virginia Harborview Medical Center, Commonwealth University, Richmond, VA, USA Seattle, WA, USA HandbookofClinicalNeurology,Vol.96(3rdseries) BacterialInfections K.L.RoosandA.R.Tunkel,Editors #2010ElsevierB.V.Allrightsreserved Chapter 1 Pathogenesis and pathophysiology of bacterial CNS infections JOHANNSELLNER1,MARTIN G.TA¨UBER2,ANDSTEPHEN L.LEIB2* 1DepartmentofNeurology, TechnischeUniversit€atM€unchen,M€unchen,Germany 2DepartmentofInfectiousDiseases, InstituteforInfectiousDiseases,University ofBern,Bern,Switzerland INTRODUCTION clinicalpresentationandtreatmentoptionsarecovered inthelaterchapters.Here,themostprevalentbacterial A bacterial infection of the central nervous system CNS infections are briefly summarized (Fig. 1.1). (CNS) is a life-threatening condition with high mortal- ity, particularly in the case of bacterial meningitis. Bacterial meningitis Antibiotic therapy and vaccines have changed the face of bacterial CNS infections, but outcome is still unfa- Bacterial meningitis is both the most common and vorable and associated with permanent neurological most serious bacterial infection of the CNS. It is char- dysfunction in many survivors. A key factor that con- acterized by acute purulent infection of the meninges tributes to this insufficient therapeutic success is our affecting the pia, the arachnoid, and subarachnoid incomplete understanding of the pathogenesis and space (van de Beek et al., 2006). The inflammatory pathophysiology of bacterial CNS infections. A central reaction may not only involve the meninges and the role of the host’s inflammatory response in causing subarachnoidspacebutalsothebrainparenchymalves- cerebral complications and associated morbidity and sels (vasculitis) and the parenchyma itself and contri- mortality has been increasingly recognized. The proto- butes to the development of neuronal injury. Systemic typical bacterial CNS infection that illustrates this is complications, including septic shock, pneumonia, bacterial meningitis, where two-thirds of meningitis- and disseminated intravascular coagulation, also con- related deaths are attributable primarily, or in part, to tribute to unfavorable outcome. CNS complications (van der Flier et al., 2003). The remainderisbelievedtoresultfromsystemiccomplica- Brain abscess tions (Pfister et al., 1993). The focus of this chapter is to summarize the cur- Abrainabscessisafocal,suppurativeinfectionwithin rentknowledgeofthefollowingpathophysiologicsteps thebrainparenchyma,typicallysurroundedbyavascu- of CNS infections: (1) mucosal colonization by the larized capsule (Sharma et al., 2000). The term cere- pathogen;(2)interactionofmicrobeswithandcrossing britis is used to describe the early nonencapsulated oftheblood–brainorblood–choroidbarrier;(3)micro- correlate.Onceinfectionisestablished,thebrainabscess bial survival and growth within the CNS; (4) induction evolvesthroughaseriesofstages.Thedynamicsofthis of CNS inflammation; (5) pathophysiologic alterations process depend on the infectious organism and the in the CNS; and (6) subsequent development of neuro- immunocompetence of the host. nal damage. The early cerebritis stage is characterized by a cen- The most important conditions caused by bacterial tral core of necrosis, perivascular accumulation of invasion of the CNS are bacterial meningitis, inflammatory cells, and edema (Fig. 1.1). During the (meningo)encephalitis, brain abscess, epidural abscess, late stage of cerebritis, growth of the necrotic center and subdural empyema (Ziai and Lewin, 2007). The can be observed due to frank pus formation. During *Correspondenceto:Dr.StephenL.Leib,InstituteforInfectiousDiseases,UniversityofBern,Friedbu¨hlstrasse51,Box61,3010 Bern,Switzerland.E-mail: [email protected],Tel.þ41-31-632-49-49, Fax þ41-31-632-35-50. 2 J. SELLNER ET AL. Fig.1.1. Schematiccoronalviewillustratingthesitesofcommonbacterialcentralnervoussysteminfections.(Adaptedfrom ZiaiandLewin,2007.) the early abscess stage, the capsule formation occurs: Suppurative thrombophlebitis this can be seen as a ring-enhancing structure on neu- Suppurative intracranial thrombophlebitis is a septic roimaging. Finally, the late capsule formation stage venous thrombosis of cortical veins and sinuses. It evolves, and this is characterized by regression of can occur as a complication of bacterial meningitis, edema and a dense collagenous capsule and marked of subdural empyema or epidural abscess, or of infec- gliosis surrounding the capsule (Fig. 1.1). tions of the facial skin, the paranasal sinuses, the middle ear, or the mastoid. Epidural abscess A cranial epidural abscess is a suppurative infection Ventriculitis occurring in the virtual space between the inner skull Ventriculitis is an infection of the ventricular system surfaceandthedura(Fig.1.1).Anepiduralabscessmay of the brain. It occurs as a complication of meningitis occurasacomplicationofcraniotomyorskullfracture,or or as a primary process, often associated with implan- asaresultofinfectionofthefrontalsinuses,middleear, tation of a cerebrospinal fluid (CSF) shunt, external mastoid,ororbit.Sincetheduraistightlyadherenttothe ventricular drain, or other intracranial devices. inner skull table, the infection has to separate the dura fromtheskulltableinordertocauseanepiduralabscess. PATHOGENESISOFBACTERIAL CNSINFECTIONS Subdural empyema Most understanding of the pathophysiology of CNS Asubduralempyemaisacollectionofpusbetweenthe infections is derived from human autopsy studies and duraandarachnoidmembranes(Fig.1.1).Themostfre- from experimental models of bacterial meningitis. quentcauseisafrontalsinusitis,eitheraloneorincom- Hence, the current understanding will be covered with bination with ethmoid and maxillary sinusitis. In these regardtoknowledgeobtainedfromclinicalandexperi- conditions, the subdural empyema results from either mental studies of bacterial meningitis. retrograde spread of infection from septic thrombo- phlebitis of the mucosal veins draining the sinuses or Most prevalent pathogens of bacterial contiguous spread of infection to the subarachnoid meningitis space from osteomyelitis in the posterior wall of the sinuses. Less frequently a subdural empyema may Here, the most common causative agents of bacterial developasacomplicationofaneurosurgicalprocedure. meningitis and the current understanding of their Often, there is concomitant epidural empyema, cortical pathogenetic mechanisms leading to mucosal coloniza- thrombophlebitis, or intracranial abscess. Involvement tion, dissemination, and traversal of the blood–brain ofveinscanalsoresultinvenouscorticalinfarction. and blood–choroid barrier are described. PATHOGENESIS AND PATHOPHYSIOLOGY OF BACTERIAL CNS INFECTIONS 3 and oligosaccharides (Tong et al., 2000). IgA protease S TREPTOCOCCUS PNEUMONIAE is a zinc metalloprotease which inactivates IgA, an S. pneumoniae is a gram-positive, a-hemolytic, cata- important component of the mucosal host defense lase-negative,andoptochin-sensitivebacterium.Itisthe (Reinholdt and Kilian, 1997). most frequent cause of community-acquired bacterial Adherence of pneumococci to mammalian cells is meningitis, except in the neonatal period (Weisfelt affectedbyphasevariations,inwhichcolonialmorphol- et al., 2006a). ogyofthepathogen shifts from opaque totransparent In S. pneumoniae, surface components, of which (Fig. 1.2). Differences in colony opacity correlate with morethan500areknowntodate,aremajoradherence differencesinvirulence(Weiseretal.,1994).Thetrans- factors (Oggioni et al., 2006). A variety of choline- parent phenotype is more capable of colonizing the binding proteins expressed on the cell surface, such nasopharynx, whereas the opaque phenotype shows as pneumococcal surface adhesin A (PsaA) and cho- increased virulence during systemic infections. Trans- line-binding protein A (CbpA; also called PspC, SpsA, parent, invasive bacteria harbor significantly greater or Hic), function as adhesins to host cells. PsaA and amountsofthepneumococcaladhesinsCbpAandmore CbpA are produced by virtually all clinical isolates cell wall choline, the natural ligand for the platelet- of S. pneumoniae and contribute to their virulence activatingfactor(PAF)receptor,whichisexpressedon (Gosink et al., 2000). Several studies have shown that endothelial cells following inflammatory activation immunization with these proteins can protect against (Cundelletal.,1995). infection with multiple pneumococcal serotypes and A key virulence factor is pneumolysin, which is a prevent nasopharyngeal carriage (Kayhty et al., 2006). product of S. pneumoniae that binds to cholesterol Moreover, in mice lacking CbpA, the most frequent in cell membranes, forming oligomers and creating Cbp, S. pneumoniae is not capable of colonizing the transmembrane pores (Hirst et al., 2004). Pneumolysin nasopharynx (Rosenow et al., 1997). Further factors triggers different proinflammatory reactions and can supporting nasopharyngeal colonization include neur- activate the classical complement pathway (Boulnois aminidase NanA and immunoglobulin (Ig) A protease. et al., 1991; Houldsworth et al., 1994). On the other NanA decreases viscosity of the mucus or exposes hand, pneumolysin also interferes with cellular func- other cell surface receptors by cleaving N-acetylneur- tions of the immune system, including the respiratory aminic acid from mucin, glycolipids, glycoproteins, burst of polymorphonuclear leukocytes, chemotaxis, Opaque phenotype Nasopharynx (encapsulated pathogen) Transparent phenotype Mucin layer Nasopharyngeal epithelial cell layer Extracellular matrix Endothelial cells Monocyte Bloodstream MMPs Neutrophils Cytokines Chemokines Integrins Selectins Blood–brain barrier Brain microvascular endothelial cells Basal membrane Tight Brain junction MMPs Glia cell Cytokines Chemokines Fig. 1.2. Schematic representation of pathogenetic steps involved in the development of bacterial meningitis. MMP, matrix metalloproteinase.
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