cns infection 11

8/6/2019 CNS Infection 11

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CNS infectionCNS infectionSupischa theerasasawatSupischa theerasasawat


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ContentContent RoutsRouts Classification by organ involvementClassification by organ involvement

MeningitisMeningitis

EncephalitisEncephalitis

MyelitisMyelitis

Classification by pathogenClassification by pathogen BacteriaBacteria

VirusVirus

TBTB

FungusFungus

SpirocheteSpirochete

ParasiteParasite


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4 routes which infectious agents can enter

the CNS

INFECTIONS

hematogenous spread

i) most common- usually via arterialroute

- can enter retrogradely(veins)

direct implantationi) most often is traumatic

ii) iatrogenic (rare) vialumbar puncture

local extension(secondary to establishedinfections)

i) most often frommastoid and frontalsinuses, infected tooth

PNS into CNSi) viruses

- rabies

- herpes zoster


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DefinitionsDefinitions

MeningitisMeningitis

Inflammation of the leptomeningesInflammation of the leptomeninges

Usually caused by bacteriaUsually caused by bacteria EncephalitisEncephalitis

Inflammation of the brain itselfInflammation of the brain itself

Caused by many types of organismsCaused by many types of organisms

MyelitisMyelitis

Inflammation of the spinal cordInflammation of the spinal cord


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Meningitis classified

acute pyogenic

usually bacterial meningitis

aseptic usually acute viral meningitis

chronic

usually TB, spirochetes, cryptococcus


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Characteristic CSF formulasCharacteristic CSF formulas


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Imaging should precede lumbar punctureImaging should precede lumbar puncture

newnew--onset seizuresonset seizures

an immunocompromised statean immunocompromised state

signs that are suspicious for spacesigns that are suspicious for space--occupying lesionsoccupying lesions

moderatemoderate--toto--severe impairment ofsevere impairment of

consciousnessconsciousness


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EncephalitisEncephalitis

Acute fluAcute flu--like prodome, high fever, severelike prodome, high fever, severe

headache, N/V,headache, N/V, altered consciousnessaltered consciousness,,

seizure and focal neurological signsseizure and focal neurological signs

Limbic encephalitis (temporal lobeLimbic encephalitis (temporal lobe

involvement)involvement)

Rhombenencephalitis (lower cranial n.Rhombenencephalitis (lower cranial n.

involvement, myoclonus, autonomicinvolvement, myoclonus, autonomic

dysfunction, lock in syndrome)dysfunction, lock in syndrome)


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BacteriaBacteria


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Examples of BacteriaExamples of Bacteria

Streptococcus pneumoniaeStreptococcus pneumoniae

Neisseria meningitidisNeisseria meningitidis

Haemophilus influenzaeHaemophilus influenzae


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PathogenesisPathogenesis


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Microorganism vary with age of the patient

a) neonatesi) E. coli

ii) Strep. pneumonia

iii) Listeria monocytogenes

b) adolescents and young adultsi) Neisseria meningitidis (most

common)

ii) Haemophilus influenza- immunizations have markedly

reduced this pathogen


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Signs & Symptoms of MeningitisSigns & Symptoms of Meningitis

Headache >Headache > 9090%%

Fever >Fever > 9090%%

Stiffness of neck >Stiffness of neck > 8585%% VomitingVomiting 3535%%

SeizuresSeizures 3030%%

WeaknessWeakness 1515%%


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Spinal tab yields

cloudy or frankly purulent CSF ( 100-

10,000 WBC)

increased pressure (4

0% presure>400mmH2O)

o neutrophils (80-95%)


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Respiratory isolation for 24 hours is indicated for patients with suspected

meningococcal infection


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Adjunctive dexamethasone therapyAdjunctive dexamethasone therapy

DexamethasoneDexamethasone does not improvedoes not improve thethe

outcomeoutcome in all adolescents and adults within all adolescents and adults with

suspected bacterial meningitis; asuspected bacterial meningitis; a

beneficial effect appears to be confined tobeneficial effect appears to be confined to

patients with microbiologically provenpatients with microbiologically proven

disease, including those who havedisease, including those who have

received prior treatment with antibioticsreceived prior treatment with antibiotics

n engl j med 357;24 www.nejm.org december 13, 2007


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Neurocritical careNeurocritical care

In patients with a high risk of brain herniation, considerIn patients with a high risk of brain herniation, considermonitoring intracranial pressure and intermittentmonitoring intracranial pressure and intermittentadministration of osmotic diuretics to maintain anadministration of osmotic diuretics to maintain an

intracranial pressure of 6060 mm Hgmm Hg

Initiate repeated lumbar puncture, lumbar drain, orInitiate repeated lumbar puncture, lumbar drain, orventriculostomy in patients with acute hydrocephalusventriculostomy in patients with acute hydrocephalus

Electroencephalographic monitoring in patients with aElectroencephalographic monitoring in patients with ahistory of seizures and fluctuating scores on thehistory of seizures and fluctuating scores on theGlasgow Coma ScaleGlasgow Coma Scale**


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Airway and respiratory careAirway and respiratory care

Intubate or provide noninvasive ventilation inIntubate or provide noninvasive ventilation in

patients with worsening consciousness (clinicalpatients with worsening consciousness (clinical

and laboratory indicators for intubation includeand laboratory indicators for intubation include

poor cough and pooling secretions, apoor cough and pooling secretions, a RR of >RR of >3535per minute, arterial oxygen saturation of


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Circulatory careCirculatory care

In patients with septic shock, administer lowIn patients with septic shock, administer lowdoses of corticosteroids (if there is a poordoses of corticosteroids (if there is a poorresponse on corticotropin testing, indicatingresponse on corticotropin testing, indicatingadrenocorticoid insufficiency, corticosteroidsadrenocorticoid insufficiency, corticosteroids

should be continued)should be continued) Initiate inotropic agents (dopamine) to maintainInitiate inotropic agents (dopamine) to maintain

blood pressure (blood pressure (mean arterial pressure,mean arterial pressure, 7070--100100mm Hg)mm Hg)

Initiate crystalloids or albumin (Initiate crystalloids or albumin (55%) to maintain%) to maintainadequate fluid balanceadequate fluid balance

Consider the use of a SwanGanz catheter toConsider the use of a SwanGanz catheter tomonitor hemodynamic measurementsmonitor hemodynamic measurements


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Other supportive careOther supportive care

Initiate nasogastricInitiate nasogastrictube feeding of atube feeding of astandard nutritionstandard nutrition

formulaformula Initiate prophylaxisInitiate prophylaxis

with protonwith proton--pumppumpinhibitorsinhibitors

MaintainMaintainnormoglycemic statenormoglycemic state((serum glucose level,serum glucose level,4040C, use cooling byC, use cooling byconduction orconduction orantipyretic agentsantipyretic agents


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Complications during the Clinical CourseComplications during the Clinical Course

and Outcomesand Outcomes


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Waterhouse-Friderichsen

syndrome

results from meningitis-associated

septicemia

- hemorrhagic infarction of the adrenal glands- cutaneous petechiae

- common with menigococcal and

pneumococcal meningitis


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ACUTE FOCAL SUPPURATIVE

INFECTIONS

Brain abscess

Subdural Empyema

Extradural Abscess


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Brain abscess

may arise from a variety of routes [often

from primary infected site in the heart

(acute bacterial endocarditis), lungs, tooth

decay, bones]

Strep and Staph are the most common

bacteria

cerebral abscesses are destructive lesions


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central liquefactive necrosis surrounded by

fibrous cap

- edema in surrounding area common sites (in descending order)

- frontal lobe

- parietal lobe- cerebellum


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present with progressive focal deficits

- signs ofo ICP

- CSF undero pressure

- WBC and protein o

- glucose normal

rupture of abscess can cause ventriculitis,

meningitis and venous sinus thrombosis surgery and antibiotics have decreased lethality

to less that 10%


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Subdural Empyema

bacteria and fungus can spread to

subdural space p subdural empyema

arachnoid and subarachnoid spaces usuallyunaffected

thrombophlebitis may develop in

bridging veins p venous occlusion and

infarct


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Clinical

febrile

headache

neck stiffness untreated may develop lethargy

and coma

CSF profile similar to abscess


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Extradural Abscess

commonly associated with osteomyelitis

usually arise from adjacent site of infection

sinusitis or a surgical procedurewhen occurring in spinal epidural

space p spinal compression

neurosurgical emergency


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VirusesViruses


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Examples of VirusesExamples of Viruses

Herpes Simplex VirusHerpes Simplex Virus


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PathogenesisPathogenesis

Depending on the virus, the pathogenesisDepending on the virus, the pathogenesis

consists of a mixture of direct viralconsists of a mixture of direct viral

pathology or postpathology or post--infectious inflammatoryinfectious inflammatory

or immuneor immune--mediated responsemediated response


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AcuteAseptic (Viral Meningitis)

refers to absence of any recognizable

organism

generally viral clinical course is less fulminant

compared to bacterial


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Spinal tab yields

CSF glucose near normal

protein only moderately elevated

lymphocytic pleocytosis usually self limiting

most common is the enterovirus


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NSAID

antibiotics

CSF is sterile glucose normal (CSF)

pleocytosis with neutrophils

o CSF protein

Drug-inducedaseptic meningitis


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Viral encephalitis

parenchymal infection meningeal inflammation and sometimes spinal cord

involvement (encephalomyelitis)

most characteristic features perivascular and parenchymal mononuclear cell

infiltration

intrauterine viral infections may cause congenitalmalformations (rubella)

slowly progressive degenerative disease may occurmany years after viral illness postencephalitic parkinsonism


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Clinical

generalized neurologic deficits

- seizures

- confusion

- delirium- stupor and coma

CSF usually colorless

- slightly o pressure

- initially a neutrophilic pleocytosis, which rapidly

- converts to lymphocytes

- proteins are o

- glucose is normal


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Herpes virus in CNSHerpes virus in CNS

EncephalitisEncephalitis HSVHSV--11//22, VZV, CMV, VZV, CMV

Acute meningitisAcute meningitis HSVHSV--22, VZV, VZV

Recurrent meningitisRecurrent meningitis HSVHSV--22MyelitisMyelitis HSVHSV--22, VZV, CMV, EBV, VZV, CMV, EBV

CombinedCombined EBVEBV

VentriculitisVentriculitis VZV, CMVVZV, CMVBrainstem encephalitisBrainstem encephalitis HSVHSV--11//22, VZV, VZV

polymyeloradiculitispolymyeloradiculitis CMVCMV


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HSV type 1 (HSV-1)

occur at any age

most common in children and young

adultsmost common S & S are mood and

memory change

most often begins in the temporal lobes

and orbital gyri of frontal lobes


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HSV type 2 (HSV-2)

in adults as meningitis

~ 50% of neonates develop severe

encephalitis to mothers having active primary genital HSV infections


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Varicella-Zoster virus (Herpes Zoster)

childhood chickenpox

reactivation in adults (i.e., shingles) painful vascular skin eruptions

usually is self limited, however may be a persistent postherpetic neuralgia syndrome

- ~ 10% of patients

overt CNS manifestations are rare however, when present do produce

more severe signs

- granulomatous arteritis


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Cytomegalovirus

occurs in fetuses and immunosupprressed

most common opportunistic viral pathogen in

patients with AID

S affects 15-20% of patients

localize in paraventricular subependymal

regions of the brain

severe hemorrhagic necrotizing


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ClinicalClinical

CMV encephalitisCMV encephalitis AcuteAcute--subacutesubacute

confusionconfusion

DisorientationDisorientation

Memory lossMemory loss

Cranial n. palsyCranial n. palsy

FeverFever

CSFCSF HypoglycorrhachiaHypoglycorrhachia

MononuclearMononuclearpleocytosispleocytosis

CMVCMVpolyradiculomyelitispolyradiculomyelitis Sacral painSacral pain

paraesthesiaparaesthesia

Sphincter dysfunctionSphincter dysfunction

Subacute onset ofSubacute onset ofascending flaccidascending flaccidparaparesisparaparesis

CSFCSF HypoglycorrhachiaHypoglycorrhachia

PMN pleocytosisPMN pleocytosis


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DiagnosisDiagnosis

CMV PCR +CMV PCR +


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TreatmentTreatment

GanciclovirGanciclovir 55 mg/kg bidmg/kg bid 33 wk + foscarnetwk + foscarnet

6060 mg/kg qmg/kg q 88 h until improvedh until improved

Maintenance ValMaintenance Val--GCVGCV 900900 mg OD

+mg OD

+foscarnetfoscarnet 9090--120120 mg IV ODmg IV OD


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TBTB


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TBTB

headaches

malaise and confusion

vomitingCSF:

moderate pleocytosis

- PMN and MN proteins markedly o

glucose slightly q or normal


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Subarachnoid space p fibrous exudate

most often at base of brain

often obliterating the cisterns

encasing cranial nerves

development of a single intraparenchymal

mass p tuberculoma

may cause significant mass effect


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Clinical

most serious is arachnoid fibrosis and

- hydrocepahlus

obliterative endarteritis- arterial occlusion and infarction

spinal cord roots may be involved


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TreatmentTreatment

2IRZE(S) + 10 IR


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TreatmentTreatment

33 IRZS +IRZS + 66IRZIRZ

Dexamethasone IVDexamethasone IV 00..44 MKDMKD 11 wk thenwk then 00..33

MKDMKD 11 wk thenwk then 00..22 MKDMKD 11 wk thenwk then 00..11

MKDMKD 11 wkwk then oralthen oral 44 mg/d tapemg/d tape 11 mg/dmg/d

withinwithin 44 wkwk


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SpirocheteSpirochete


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Neurosyphilis

tertiary stage ~ 10% of untreated patients

major forms of meningovascular neurosyphilis are

paretic, and tabes dorsalis meningovascular neurosyphilis is chronic meningitis

involving base of the brain, spinal leptomeninges andcerebral convexities. Obliterative endarteritis (Heubnerarteritis)

paretic neurosyphilis caused by invasion of the brain byT. pallidum. Progressive loss of mental and physicalfunctions with mood alterations

Tabes dorsalis is a result of damage by the spirochete tothe sensory nerves in dorsal roots, causing locomotor

ataxia and sense of position, loss of pain sensation


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DiagnosisDiagnosis

CSF reactive FTACSF reactive FTA--ABS or TPHAABS or TPHA


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TreatmentTreatment

Penicillin G IVPenicillin G IV 44 mU qmU q 44 hh 1414d thend then

benzathine penicillin Gbenzathine penicillin G 22..44 mU IM xmU IM x33


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FungiFungi


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Example of a FungusExample of a Fungus

Cryptococcus neoformansCryptococcus neoformans


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ClinicalClinical

FeverFever

HeadacheHeadache

Stiffness of neck positiveStiffness of neck positive Sign of increase ICPSign of increase ICP


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DiagnosisDiagnosis

Indian inkIndian ink

Cryptococcal AgCryptococcal Ag


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TreatmentTreatmentdiseasedisease protocalprotocal dosedose durationduration

HIV neg.HIV neg. 11 AmphotericinAmphotericin 00..77MKDMKD

+flucytosine+flucytosine 100100MKDMKD

+fluconazole+fluconazole 400400mg/dmg/d

22 wkwk

1010 wkwk

22 AmphotericinAmphotericin 00..77MKDMKD

+flucytosine+flucytosine 100100MKDMKD

1010 wkwk

HIV pos.HIV pos.

inductioninduction

AmphotericinAmphotericin 00..77MKDMKD

+flucytosine+flucytosine 100100MKDMKD+fluconazole+fluconazole 400400mg/dmg/d

22 wkwk

1010 wkwk

maintanancemaintanance FluconazoleFluconazole 400400 mg/dmg/d


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ParasitesParasites


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Examples of ParasitesExamples of Parasites

Toxoplasma gondiiToxoplasma gondii


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ClinicalClinical

Subacute tSubacute t00 chronic feverchronic fever

HeadacheHeadache

Focal neurodeficit correlate withFocal neurodeficit correlate withanatomical site involvement (anatomical site involvement (basal gangliabasal ganglia

and corticomedullary junctionand corticomedullary junction))


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DiagnosisDiagnosis

DefiniteDefinite tissue biopsytissue biopsy

AntiAnti--toxplasma IgGtoxplasma IgG

Clinical compatible+ imagingClinical compatible+ imaging


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TreatmentTreatment

PyrimethaminePyrimethamine 200200

mg thenmg then 5050--7575 mg +mg +

sulfadiazinesulfadiazine 11--11..55g qg q

66 h + folinic acidh + folinic acid 1515mg OD at leastmg OD at least 66

weeksweeks

Pyrimethamine +Pyrimethamine +

folinic acidfolinic acid

ClindamycinClindamycin 600600 mg qmg q

66 hh AzithromycinAzithromycin 900900--

12001200 mg ODmg OD

Cotrimoxazole (Cotrimoxazole (55

mg/kg TMP) bidmg/kg TMP) bid


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Secondary prophylaxisSecondary prophylaxis

PyrimethaminePyrimethamine 2525--5050 mg + sulfadiazinemg + sulfadiazine

00..55--11g qg q 66 h + folinic acidh + folinic acid 1515 mg ODmg OD

PyrimethaminePyrimethamine 2525--5050 mg + clindamycinmg + clindamycin

600600 mg qmg q 66 h + folinic acidh + folinic acid 1515 mg ODmg OD

Stop CDStop CD44 >> 200200 >> 66 mo.mo.

cns infection 11

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