Bacterial Infections of the Central Nervous System

273 Pages·2010·23.189 MB·English

by  Karen L. Roos and Allan R. Tunkel (Eds.)

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
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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.