Bacterial and NonBacterial and Non--Bacterial CNS Bacterial CNS InfectionsInfections

EMERGENCY NEUROLOGY LECTURE EMERGENCY NEUROLOGY LECTURE SERIES SERIES

  

JULY 7, 2010JULY 7, 2010

DrDr. . Abdullah AlAbdullah Al--Salti R3Salti R3

CNS INFECTIONSCNS INFECTIONSOverviewOverview

Life-threatening problems with high associated Life-threatening problems with high associated mortality and morbidity.mortality and morbidity.

Presentation may be acute, subacute, or chronic.Presentation may be acute, subacute, or chronic.

Clinical findings determined by anatomic site(s) of Clinical findings determined by anatomic site(s) of involvement, infecting pathogen, and host response.involvement, infecting pathogen, and host response.

Vulnerability of CNS to the effects of inflammation & Vulnerability of CNS to the effects of inflammation & edema mandates prompt diagnosis with appropriate edema mandates prompt diagnosis with appropriate therapy if consequences to be minimized.therapy if consequences to be minimized.

CNS INFECTIONSCNS INFECTIONSOUT LINE OUT LINE

1.1. Bacterial meningitisBacterial meningitis

2.2. Aseptic Meningitis Aseptic Meningitis

3.3. Viral MeningitisViral Meningitis

4.4. Viral encephalitisViral encephalitis

CNS InfectionsCNS Infections

MeningitisMeningitis• Bacterial, viral, fungal, chemical, Bacterial, viral, fungal, chemical,

carcinomatouscarcinomatous EncephalitisEncephalitis

• Bacterial, viralBacterial, viral MeningoencephalitisMeningoencephalitis AbscessAbscess

• Parenchymal, subdural, epiduralParenchymal, subdural, epidural

INFECTIONS 4 routes which infectious agents can enter the CNS

a) hematogenous spreadi) most common

- usually via arterial route- can enter retrogradely (veins)

b) direct implantationi) most often is traumaticii) iatrogenic (rare) via lumbar punctureiii) congenital (meningomyelocele)

c) local extension (secondary to established infections) i) most often from mastoid, frontal sinuses, infected

tooth, etc.d) PNS into CNS

i) viruses- rabies- herpes zoster

BACTERIAL MENINGITISBACTERIAL MENINGITIS Meningitis

refers to an inflammatory process of leptomeninges and CSF.

Meningoencephalitisrefers to inflammation to meninges and brain parenchyma.

Meningitis classified:a) acute pyogenic

i) usually bacterial meningitisb) aseptic

i) usually acute viral meningitisc) chronic

i) usually TB, spirochetes, cryptococcus.

Incidence of 3 cases/100,000 population/yr (~25,000 total cases).

COMMON BACTERIAL PATHOGENS BASED ON COMMON BACTERIAL PATHOGENS BASED ON PREDISPOSING FACTOR IN PATIENTS WITH PREDISPOSING FACTOR IN PATIENTS WITH

MENINGITISMENINGITISPredisposing FactorPredisposing Factor

AgeAge 0-4 wk0-4 wk

4-12 wk4-12 wk

3 mo to 18 yr3 mo to 18 yr

18-50 yr18-50 yr

>50 yr>50 yr

Common Bacterial PathogensCommon Bacterial Pathogens

Streptococcus agalactiae, Escherichia coli,Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, KlebsiellaListeria monocytogenes, Klebsiella pneumoniae, Enterococcus pneumoniae, Enterococcus sppspp., Salmonella ., Salmonella

sppspp..

S. agalactiae, E. coli, L. monocytogenes, S. agalactiae, E. coli, L. monocytogenes, Haemophilus influenzae, Streptococcus Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidispneumoniae, Neisseria meningitidis

H. influenzae, N. meningitidis, S. pneumoniaeH. influenzae, N. meningitidis, S. pneumoniae

S. pneumoniae, N. meningitidisS. pneumoniae, N. meningitidis

S. pneumoniae, N. meningitidis, LS. pneumoniae, N. meningitidis, L. . monocytogenesmonocytogenes, aerobic gram-negative bacilli , aerobic gram-negative bacilli

Clinical FeaturesClinical Features

Signs and symptoms:Signs and symptoms: rapid onset of fever rapid onset of fever headacheheadache photophobiaphotophobia nuchal rigiditynuchal rigidity lethargy, malaise lethargy, malaise altered mentation altered mentation seizureseizure vomiting.vomiting.

van de Beek D, de Gans J, Tunkel AR, et al .Community-acquired bacterial meningitisin adults. N Engl J Med 2006;354(1):44–53.

Clinical FeaturesClinical Features Study of 493 adult patients with bacterial meningitis, Study of 493 adult patients with bacterial meningitis,

the presence of the ‘‘classic triad’’ of the presence of the ‘‘classic triad’’ of feverfever, , neck neck stiffnessstiffness, and , and altered mental statusaltered mental status was present in two- was present in two-thirds of patients.thirds of patients.

feverfever WAS the most common element, in 95%. WAS the most common element, in 95%.

((N Engl J Med 1993;328(1):21–8N Engl J Med 1993;328(1):21–8. ). )

Older patients with S. pneumoniae meningitis are more Older patients with S. pneumoniae meningitis are more likely to have the classic triad.likely to have the classic triad.

Weisfelt M, van de Beek D, Spanjaard L, et al. Community-acquired Weisfelt M, van de Beek D, Spanjaard L, et al. Community-acquired bacterial meningitis in older people. J Am Geriatr Soc bacterial meningitis in older people. J Am Geriatr Soc 2006;54(10):1500–7.2006;54(10):1500–7.

Other studies have shown the classic triad to be less Other studies have shown the classic triad to be less common, with estimates ranging from 21% to 51%.common, with estimates ranging from 21% to 51%.

All cases studied had at least one of the three signs; the All cases studied had at least one of the three signs; the absence of the all components of the classic triad excludes the absence of the all components of the classic triad excludes the diagnosis in immunocompetent individuals.diagnosis in immunocompetent individuals.

Physical examinationPhysical examination A careful neurological examination is important to evaluate for :A careful neurological examination is important to evaluate for :

• focal deficits focal deficits • increased intracranial pressure (ICP). increased intracranial pressure (ICP).

Examination should include assessment for meningeal irritationExamination should include assessment for meningeal irritation• Brudzinski’s sign Brudzinski’s sign • Kernig’s sign Kernig’s sign

findings include purpura or petechia of the skin, which may occur findings include purpura or petechia of the skin, which may occur with meningococcemia.with meningococcemia.

Bacterial meningitisBacterial meningitis

InvestigationsInvestigations

LPLP

Single most impt diagnostic test.Single most impt diagnostic test. Mandatory, esp if bacterial meningitis Mandatory, esp if bacterial meningitis

suspected.suspected.

Tube #1 – glucose and proteinTube #1 – glucose and protein Tube #2 – cell count and differentialTube #2 – cell count and differential Tube #3 – gram stain and rountine culture, Tube #3 – gram stain and rountine culture,

cyrptococcal antigen, AFB stain and culturecyrptococcal antigen, AFB stain and culture Tube #4 – VDRL, or viral studies (PCR)Tube #4 – VDRL, or viral studies (PCR)

CSF CharacteristicsCSF CharacteristicsBacterialBacterialViralViralFungalFungalTBTB

Opening Opening PressurePressure

ElevatedElevatedSlight Slight elevatedelevated

Normal Normal or Highor High

Usually Usually highhigh

GlcGlcLowLowNormalNormal LowLowLowLow

ProProVery Very highhigh

NormalNormal HighHighHighHigh

RbcsRbcsFewFewNoneNoneNoneNoneNoneNone

Wbcs Wbcs (c/mm3)(c/mm3)

>>200200<<200200<<505020-3020-30

DiffDiffPMNsPMNsMonoMonoMonoMono MonoMono

CT Before LP in Patients with CT Before LP in Patients with Suspected MeningitisSuspected Meningitis

301 pts with suspected meningitis; 235 301 pts with suspected meningitis; 235 (78%) had CT prior to LP(78%) had CT prior to LP

CT abnormal in 56/235 (24%); 11 pts (5%) CT abnormal in 56/235 (24%); 11 pts (5%) had evidence of mass effecthad evidence of mass effect

Features associated with abnl. CT were:Features associated with abnl. CT were:• age >60, age >60, • immunocompromise, immunocompromise, • H/O CNS dz, H/O CNS dz, • H/O seizure w/in 7d, & H/O seizure w/in 7d, & • selected neuro abnlsselected neuro abnls

Hasbun, NEJM Hasbun, NEJM 2001;345:17272001;345:1727

CT head Before LPCT head Before LP(Cont.)(Cont.) Neuro abnls included Neuro abnls included altered MSaltered MS, , inability to inability to

answer 2 consecutive questions or follow 2 answer 2 consecutive questions or follow 2 consecutive commandsconsecutive commands, , gaze palsygaze palsy, , abnl visual abnl visual fieldsfields, , facial palsyfacial palsy, , arm or leg driftarm or leg drift, & , & abnl abnl languagelanguage

96/235 pts (41%) who underwent CT had none of 96/235 pts (41%) who underwent CT had none of features present at baselinefeatures present at baseline

CT normal in 93 of these 96 pts (NPV 97%).CT normal in 93 of these 96 pts (NPV 97%).

Of the 3 remaining patients, only 1 had mild mass Of the 3 remaining patients, only 1 had mild mass effect on CT, and all 3 underwent lumbar puncture effect on CT, and all 3 underwent lumbar puncture with no evidence of brain herniationwith no evidence of brain herniation

Hasbun, NEJM 2001;345:1727Hasbun, NEJM 2001;345:1727

Consideration for lumbar puncture Consideration for lumbar puncture without neuroimagingwithout neuroimaging

David Somand, MDa,WilliamMeurer, MDDavid Somand, MDa,WilliamMeurer, MD Department of Emergency Medicine, University of Michigan, Taubman Center B1354

SPC #5303, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5303, USA Department of Neurology, University of Michigan, Taubman Center 1914 SPC #5316, 1500 E.

Medical Center Drive, Ann Arbor, MI 48109-5316, USA

Age less than 60Age less than 60 ImmunocompetentImmunocompetent No history of CNS diseaseNo history of CNS disease No recent seizure (less than 1 week)No recent seizure (less than 1 week) Normal sensorium and cognitionNormal sensorium and cognition No papilledemaNo papilledema No focal neurologic defecitsNo focal neurologic defecits

Acute bacterail meninigitsAcute bacterail meninigitsMRIMRI

Not generally useful in acute diagnosis Not generally useful in acute diagnosis (Pt cooperation; logistics).(Pt cooperation; logistics).

Very helpful in investigating potential Very helpful in investigating potential complications developing later in complications developing later in clinical course such as venous sinus clinical course such as venous sinus thrombosis or subdural empyema.thrombosis or subdural empyema.

Laboratory Testing Helpful in DistinguishingLaboratory Testing Helpful in DistinguishingBacterial from Viral MeningitisBacterial from Viral Meningitis..

CSF lactate .CSF lactate . Elevated CSF lactate concentrations may be useful in differentiating Elevated CSF lactate concentrations may be useful in differentiating

bacterial from nonbacterial meningitis in patients who have not bacterial from nonbacterial meningitis in patients who have not received prior antimicrobial therapy. received prior antimicrobial therapy.

study of 78 patients with acute meningitis in which CSF lactate study of 78 patients with acute meningitis in which CSF lactate concentrations of >4.2mmol/L were considered to be a positive concentrations of >4.2mmol/L were considered to be a positive discriminative factor for bacterial meningitis .discriminative factor for bacterial meningitis .

SensSens SpecSpec PPVPPV NPVNPV 96%, 100%, 100%, 97%. 96%, 100%, 100%, 97%.

Furthermore, other factors (e.g., cerebralhypoxia/ischemia, Furthermore, other factors (e.g., cerebralhypoxia/ischemia, anaerobic glycolysis,vascular compromise,and metabolism of CSF anaerobic glycolysis,vascular compromise,and metabolism of CSF leukocytes) also may elevateCSF lactate concentrations. leukocytes) also may elevateCSF lactate concentrations.

Therefore, measurement of CSF lactate concentrations is not Therefore, measurement of CSF lactate concentrations is not recommended for patients with suspected community-acquired recommended for patients with suspected community-acquired bacterial meningitis.bacterial meningitis.

Practice Guidelines for the Management of Bacterial Meningitis

Allan R. Tunkel,1 Barry J. Hartman,2 Sheldon L. Kaplan,3 Bruce A. Kaufman,4 Karen L. Roos,5 W. Michael Scheld,6and Richard J. Whitley7

Laboratory Testing Helpful in DistinguishingLaboratory Testing Helpful in DistinguishingBacterial from Viral MeningitisBacterial from Viral Meningitis..

C-reactive protein (CRP).C-reactive protein (CRP). Serum CRP concentrations were capable of Serum CRP concentrations were capable of

distinguishing Gram stain–negative bacterial distinguishing Gram stain–negative bacterial meningitis, with a sensitivity of 96%, a specificity of meningitis, with a sensitivity of 96%, a specificity of 93%, and a negative predictive value of 99%.93%, and a negative predictive value of 99%.

Measurement of serum CRP concentration may be Measurement of serum CRP concentration may be helpful in considering withholding antimicrobial helpful in considering withholding antimicrobial therapy, on the basis of the data showing that a therapy, on the basis of the data showing that a normal CRP has a high negative predictive value in normal CRP has a high negative predictive value in the diagnosis of bacterial meningitis. Provided the the diagnosis of bacterial meningitis. Provided the CSF Gram stain result is negative.CSF Gram stain result is negative.

Practice Guidelines for the Management of Bacterial MeningitisAllan R. Tunkel,1 Barry J. Hartman,2 Sheldon L. Kaplan,3 Bruce A.

Kaufman,4 Karen L. Roos,5 W. Michael Scheld,6and Richard J. Whitley7

Laboratory Testing Helpful in DistinguishingLaboratory Testing Helpful in DistinguishingBacterial from Viral MeningitisBacterial from Viral Meningitis..

procalcitonin concentration.procalcitonin concentration. Elevated serum concentrations of the polypeptide procalcitonin, Elevated serum concentrations of the polypeptide procalcitonin,

which are observed in patients with severe bacterial infection, which are observed in patients with severe bacterial infection, were shown to be useful in differentiating between bacterial and were shown to be useful in differentiating between bacterial and viral meningitis .viral meningitis .

In a study of 59 consecutive children hospitalized for meningitis , In a study of 59 consecutive children hospitalized for meningitis , the sensitivity of measurements of the serum procalcitonin the sensitivity of measurements of the serum procalcitonin concentration (using a cutoff of 15.0 mg/L) for the diagnosis of concentration (using a cutoff of 15.0 mg/L) for the diagnosis of bacterial meningitis was 94%, and the specificity was 100%. bacterial meningitis was 94%, and the specificity was 100%.

In adults, serum concentrations 10.2 ng/mL had a sensitivity and In adults, serum concentrations 10.2 ng/mL had a sensitivity and specificity of up to 100% for the diagnosis of bacterial meningitis .specificity of up to 100% for the diagnosis of bacterial meningitis .

At present, because measurement of serum procalcitonin At present, because measurement of serum procalcitonin concentrations is not readily available in clinical laboratories, concentrations is not readily available in clinical laboratories, recommendations on its use cannot be made at this time.recommendations on its use cannot be made at this time.

Practice Guidelines for the Management of Bacterial MeningitisAllan R. Tunkel,1 Barry J. Hartman,2 Sheldon L. Kaplan,3 Bruce A. Kaufman,4 Karen L. Roos,5 W.

Michael Scheld,6and Richard J. Whitley7

Laboratory Testing Helpful in DistinguishingLaboratory Testing Helpful in DistinguishingBacterial from Viral MeningitisBacterial from Viral Meningitis..

PCR. PCR. In patients who present with acute meningitis, an important In patients who present with acute meningitis, an important

diagnostic consideration is whether the patient has enteroviral diagnostic consideration is whether the patient has enteroviral meningitis. meningitis.

Enteroviral RT-PCR has been tested in clinical settings by Enteroviral RT-PCR has been tested in clinical settings by

numerous investigators and has been found to be more numerous investigators and has been found to be more sensitive than viral culture for the detection of enterovirus, with sensitive than viral culture for the detection of enterovirus, with a sensitivity and specificity of 86%–100% and 92%–100%, a sensitivity and specificity of 86%–100% and 92%–100%, respectively. respectively.

lead to shortened patient hospitalization, decreased use of lead to shortened patient hospitalization, decreased use of

antimicrobial therapy for treatment of bacterial meningitis, and antimicrobial therapy for treatment of bacterial meningitis, and reduced need for ancillary diagnostic tests .reduced need for ancillary diagnostic tests .

Practice Guidelines for the Management of Bacterial MeningitisAllan R. Tunkel,1 Barry J. Hartman,2 Sheldon L. Kaplan,3 Bruce A. Kaufman,4 Karen L. Roos,5 W.

Michael Scheld,6and Richard J. Whitley7

BACTERIAL MENINGITISBACTERIAL MENINGITIS

ManagementsManagements

APPROACH TO THE PATIENT WITH SUSPECTED APPROACH TO THE PATIENT WITH SUSPECTED MENINGITISMENINGITIS

Decision-Making Within the First 30 MinutesDecision-Making Within the First 30 Minutes

Clinical AssessmentClinical Assessment

Mode of presentationMode of presentation Acute (< 24 hrs)Acute (< 24 hrs) Subacute (< 7 days)Subacute (< 7 days) Chronic (> 4 wks)Chronic (> 4 wks)

Historical/physical exam cluesHistorical/physical exam clues Clinical status of the patient (ABCD)Clinical status of the patient (ABCD)

Integrity of host defensesIntegrity of host defenses

Management algorithm for adults with suspected bacterial meningitis.Management algorithm for adults with suspected bacterial meningitis.Practice Guidelines for the Management of Bacterial Meningitis

Overall Goals in ManagementOverall Goals in Management

1.1. To promptly recognize the patient with an To promptly recognize the patient with an acute CNS infection syndromeacute CNS infection syndrome

2. To rapidly initiate appropriate empiric 2. To rapidly initiate appropriate empiric

therapytherapy

3. To rapidly and specifically identify the 3. To rapidly and specifically identify the

etiologic agent, adjusting therapies as etiologic agent, adjusting therapies as

indicatedindicated

4.4. To optimize management of complicatingTo optimize management of complicating featuresfeatures

BACTERIAL MENINGITISBACTERIAL MENINGITISAntimicrobial RxAntimicrobial Rx

Therapy is generally IV, high dose, & bolus.Therapy is generally IV, high dose, & bolus.

Dosing intervals should be appropriate for Dosing intervals should be appropriate for drug being administered.drug being administered.

Utilize “cidal” therapy whenever possible.Utilize “cidal” therapy whenever possible.

Initiate therapy promptly (ie, within 30 mins)Initiate therapy promptly (ie, within 30 mins)

THE THERAPY OF MENINGITISTHE THERAPY OF MENINGITISCNS PenetrationCNS Penetration

Good DiffusionGood Diffusion• PenicillinsPenicillins• 33rd & 4thrd & 4th Gen Cephs Gen Cephs• ChloramphenicolChloramphenicol• RifampinRifampin• TSXTSX

Poor DiffusionPoor Diffusion• Early Gen CephsEarly Gen Cephs• ClindamycinClindamycin• AMGsAMGs• TetracyclinesTetracyclines• MacrolidesMacrolides

EMPIRIC THERAPY OF MENINGITIS IN THE EMPIRIC THERAPY OF MENINGITIS IN THE ADULTADULT

Clinical SettingClinical Setting Likely PathogensLikely Pathogens TherapyTherapy

Community-acquiredCommunity-acquired S. pneumoniaeS. pneumoniae Ceftriaxone Ceftriaxone

N. meningitidisN. meningitidis 2 gm q12h 2 gm q12h

[Listeria][Listeria] + +

[H. influenzae][H. influenzae] Vancomycin 1-2 gm 12h Vancomycin 1-2 gm 12h

+/-+/-

Ampicillin 2 gm q4hAmpicillin 2 gm q4h

Closed head traumaClosed head trauma S. pneumoniaeS. pneumoniae Pen G 3-4 mu q4h Pen G 3-4 mu q4h

StreptococciStreptococci + + Vancomycin 1-2 gm q12h Vancomycin 1-2 gm q12h

EMPIRIC THERAPY OF MENINGITIS IN THE EMPIRIC THERAPY OF MENINGITIS IN THE ADULTADULT

Clinical SettingClinical Setting Likely PathogensLikely Pathogens TherapyTherapy

High risk patientsHigh risk patients S. aureusS. aureus Vancomycin 2-3 gm/d Vancomycin 2-3 gm/d Compromised hostsCompromised hosts Gram negativeGram negative + + NeurosurgicalNeurosurgical bacilli bacilli Ceftazidime 2 gm Ceftazidime 2 gm

q8h orq8h or Open head injuryOpen head injury ListeriaListeria Cefepime 2 gm q8h Cefepime 2 gm q8h NosocomialNosocomial [Ceftriaxone 2 gm [Ceftriaxone 2 gm

q12h]q12h] ElderlyElderly [Cefotaxime 2 gm q4h] [Cefotaxime 2 gm q4h] +/-+/-

Ampicillin 2 gm q4hAmpicillin 2 gm q4h

SPECIFIC THERAPY FOR KNOWN PATHOGENSSPECIFIC THERAPY FOR KNOWN PATHOGENS

PathogenPathogen Recommended TherapyRecommended Therapy

S. pneumoniae*S. pneumoniae* Pen G 18-24 mu/dPen G 18-24 mu/d

N. meningitidisN. meningitidis oror

StreptococciStreptococci Ampicillin 12 gm/dAmpicillin 12 gm/d

[Chloro 75-100 mg/kg/d][Chloro 75-100 mg/kg/d]

[Ceftriaxone 2-4 gm/d][Ceftriaxone 2-4 gm/d]

H. influenzaeH. influenzae Cefotaxime 12 gm/dCefotaxime 12 gm/d

[Ceftriaxone 2-4 gm/d][Ceftriaxone 2-4 gm/d]

Group B strepGroup B strep Pen G 18-24 mu/dPen G 18-24 mu/d

oror

Ampicillin 12 gm/dAmpicillin 12 gm/d

[plus aminoglycoside][plus aminoglycoside]

SPECIFIC THERAPY FOR KNOWN PATHOGENSSPECIFIC THERAPY FOR KNOWN PATHOGENS(continued)(continued)

S. aureusS. aureus Nafcillin 12 gm/dNafcillin 12 gm/d

[Vancomycin 2-3 gm/d][Vancomycin 2-3 gm/d]

ListeriaListeria Ampicillin 12 gm/dAmpicillin 12 gm/d

oror

Pen G 18-24 mu/dPen G 18-24 mu/d

[plus aminoglycoside][plus aminoglycoside]

Gram negativeGram negative Cefotaxime 12 gm/dCefotaxime 12 gm/d

bacillibacilli [Ceftriaxone 2-4 gm/d][Ceftriaxone 2-4 gm/d]

PseudomonasPseudomonas Ceftazidime 6-8 gm/d orCeftazidime 6-8 gm/d or

Cefepime 6 gm/dCefepime 6 gm/d

[plus aminoglycoside][plus aminoglycoside]

BACTERIAL MENINGITISBACTERIAL MENINGITISDuration of ATB RxDuration of ATB Rx

Pathogen Duration of Rx (d)Pathogen Duration of Rx (d)

H. influenzae 7H. influenzae 7

N. meningitidis 7N. meningitidis 7

S. pneumoniae 10-14S. pneumoniae 10-14

L. monocytogenes 14-21L. monocytogenes 14-21

Group B strep 14-21Group B strep 14-21

GNRs 21GNRs 21 NEJ1997;336:708NEJ1997;336:708

CORTICOSTEROIDS AND MENINGITISCORTICOSTEROIDS AND MENINGITIS Role of steroids still somewhat uncertain.Role of steroids still somewhat uncertain.

Recent European study in adults suggested that Recent European study in adults suggested that Rx with dexa associated with ↓ in risk of Rx with dexa associated with ↓ in risk of unfavorable outcome (25%→15%, RR 0.59) & in unfavorable outcome (25%→15%, RR 0.59) & in mortality (15%→7%, RR for death 0.48).mortality (15%→7%, RR for death 0.48).

Benefit primarily pts w/S. pneumo.Benefit primarily pts w/S. pneumo.

Dose of dex was 10mg IV q6h X 4d; per Dose of dex was 10mg IV q6h X 4d; per protocol, dex given concurrent with or 15-20 protocol, dex given concurrent with or 15-20 mins before 1mins before 1stst dose of ATBs. dose of ATBs.

CORTICOSTEROIDS AND MENINGITISCORTICOSTEROIDS AND MENINGITIS(Cont)(Cont)

Only pts with cloudy CSF, + CSF GmS, or Only pts with cloudy CSF, + CSF GmS, or CSF WBC count >1000 were enrolledCSF WBC count >1000 were enrolled

Accompanying editorial raised concerns Accompanying editorial raised concerns about use of steroids in pts with DRSP about use of steroids in pts with DRSP who are being Rx’ed with vanc b/o ↓ in who are being Rx’ed with vanc b/o ↓ in CNS conc of vanc with concurrent steroid CNS conc of vanc with concurrent steroid use.use.

Practically speaking, almost all pts with Practically speaking, almost all pts with presumed bacterial meningitis are presumed bacterial meningitis are

candidates for at least 1 dose of dexa candidates for at least 1 dose of dexa NEJM 2002;347:1549NEJM 2002;347:1549

Acute bacterial meningitisAcute bacterial meningitis Antibiotic prophylaxis

Is recommended for high-risk exposures to patients with Neisseria or Hib meningitis.(potentially share secretions).

Regimens include : single-dose ciprofloxacin or ceftriaxone. rifampin 600 mg every 12 hours for five doses.

There is no indication for prophylaxis for exposure to pneumococcal meningitis.

Quinolone resistance has been reported to Neisseria, and this class of antibiotics is no longer recommended for prophylaxis in parts of the United States.

David Somand, MDa,WilliamMeurer, MDDavid Somand, MDa,WilliamMeurer, MD Department of Emergency Medicine, University of Michigan, Taubman Center B1354

SPC #5303, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5303, USA Department of Neurology, University of Michigan, Taubman Center 1914 SPC #5316, 1500 E.

Medical Center Drive, Ann Arbor, MI 48109-5316, USA

PREDICTORS OF ADVERSE CLINICAL OUTCOMES IN PREDICTORS OF ADVERSE CLINICAL OUTCOMES IN PTS WITH COMMUNITY-ACQUIRED BACTERIAL PTS WITH COMMUNITY-ACQUIRED BACTERIAL

MENINGITISMENINGITIS

Retrospecitve study; 269 pts (84% culture +).Retrospecitve study; 269 pts (84% culture +).

Adverse clinical outcome in 36% of pts(Death 27%, neuro deficit Adverse clinical outcome in 36% of pts(Death 27%, neuro deficit 9%).9%).

↓↓BP, altered MS, and seizures on presentation all independently BP, altered MS, and seizures on presentation all independently associated with adverse clinical outcome.associated with adverse clinical outcome.

Adverse outcomes in 5% of low risk pts (0 features), 37% of Adverse outcomes in 5% of low risk pts (0 features), 37% of intermediate risk pts (1 feature), and 63% of high risk pts (2-3 intermediate risk pts (1 feature), and 63% of high risk pts (2-3 features).features).

Delay in administration of appropriate ATB Rx also associated Delay in administration of appropriate ATB Rx also associated with adverse clinical outcome.with adverse clinical outcome.

Aronin et al, AIM1998;129:862Aronin et al, AIM1998;129:862

Aseptic Meningitis

Aseptic MeningitisAseptic Meningitis

All non-bacterial causes of meningitisAll non-bacterial causes of meningitis Typically less ill appearing than bacterial Typically less ill appearing than bacterial

meningitismeningitis Most common cause is viralMost common cause is viral

• HSVHSV Consider especially in infants presenting with seizureConsider especially in infants presenting with seizure Usually HSV type IIUsually HSV type II Treat with acyclovirTreat with acyclovir

• Enterovirus (coxsackie, echovirus)Enterovirus (coxsackie, echovirus) Typically occurs during late summer and fallTypically occurs during late summer and fall Spread via respiratory secretions and fecal-oralSpread via respiratory secretions and fecal-oral Affects all agesAffects all ages Generally self-limited illnessGenerally self-limited illness

Aseptic MeningitisAseptic Meningitis Other ViralOther Viral

• HIVHIV• Lymphocytic choriomeningitis virusLymphocytic choriomeningitis virus• ArbovirusArbovirus• MumpsMumps• CMVCMV• EBVEBV• VZVVZV• AdenovirusAdenovirus• MeaslesMeasles• RubellaRubella• RotavirusRotavirus• Influenza and parainfluenzaInfluenza and parainfluenza

Aseptic MeningitisAseptic Meningitis

Other infectiousOther infectious• Borrelia burgdorferiBorrelia burgdorferi• Mycobacterium tuberculosisMycobacterium tuberculosis• Treponema pallidumTreponema pallidum• Mycoplasma pneumoniaeMycoplasma pneumoniae• Rickettsia, erlichia, brucellaRickettsia, erlichia, brucella• Chlamydia Chlamydia

Aseptic MeningitisAseptic Meningitis

FungalFungal• CryptococcusCryptococcus• CoccidiodesCoccidiodes• HistoplasmosisHistoplasmosis

ParasiticParasitic• AngiostrongylusAngiostrongylus• ToxoplasmosisToxoplasmosis

Aseptic MeningitisAseptic Meningitis MedicationMedication

• NSAID’s NSAID’s • BactrimBactrim• PyridiumPyridium

MalignancyMalignancy• Lymphoma and leukemiaLymphoma and leukemia• Metastatic carcinomaMetastatic carcinoma

AutoimmuneAutoimmune• SarcoidSarcoid• Behcet’sBehcet’s• SLESLE

Viral MeningitisViral Meningitis Very commonVery common• clinical course is less fulminant compared to clinical course is less fulminant compared to

bacterialbacterial

Often caused by enterovirusesOften caused by enteroviruses

PoliovirusesPolioviruses CoxsackievirusesCoxsackieviruses EchovirusesEchoviruses

Treatment is supportiveTreatment is supportive

VIRAL ENCEPHALITISVIRAL ENCEPHALITIS

IntroductionIntroduction Encephalitis is an acute inflammatory process Encephalitis is an acute inflammatory process

affecting the brainaffecting the brain Viral infection is the most common and important Viral infection is the most common and important

cause, with over 100 viruses implicated worldwidecause, with over 100 viruses implicated worldwide Symptoms Symptoms

• FeverFever• HeadacheHeadache• Behavioral changesBehavioral changes• Altered level of consciousnessAltered level of consciousness• Focal neurologic deficitsFocal neurologic deficits• SeizuresSeizures

Incidence of 3.5-7.4 per 100,000 persons per yearIncidence of 3.5-7.4 per 100,000 persons per year

VIRAL ENCEPHALITISVIRAL ENCEPHALITIS

EnterovirusesEnteroviruses

PoliovirusesPolioviruses

CoxsackievirusesCoxsackieviruses

EchovirusesEchoviruses

TogavirusesTogaviruses Eastern equineEastern equine

Western equineWestern equine

Venezuelan equineVenezuelan equine

St. LouisSt. Louis

PowassonPowasson

CaliforniaCalifornia

West NileWest Nile

HerpesvirusesHerpesviruses

Herpes simplexHerpes simplex

Varicella-zosterVaricella-zoster

Epstein BarrEpstein Barr

CytomegalovirusCytomegalovirus

Myxo/paramyxovirusesMyxo/paramyxoviruses Influenza/parainfluenzaeInfluenza/parainfluenzae

MumpsMumps

MeaslesMeasles

MiscellaneousMiscellaneous AdenovirusesAdenoviruses

LCMLCM

RabiesRabies

HIV HIV

Patient HistoryPatient History Detailed history critical to determine the likely cause of Detailed history critical to determine the likely cause of

encephalitis. encephalitis. Prodromal illness, recent vaccination, development of few Prodromal illness, recent vaccination, development of few

days → Acute Disseminated Encephalomyelitis (ADEM) .days → Acute Disseminated Encephalomyelitis (ADEM) . Biphasic onset: systemic illness then CNS disease → Biphasic onset: systemic illness then CNS disease →

Enterovirus encephalitis. Enterovirus encephalitis. Abrupt onset, rapid progression over few days → HSE.Abrupt onset, rapid progression over few days → HSE. Recent travel and the geographical context: Recent travel and the geographical context:

• Africa → Cerebral malariaAfrica → Cerebral malaria• Asia → Japanese encephalitisAsia → Japanese encephalitis• High risk regions of Europe and USA → Lyme diseaseHigh risk regions of Europe and USA → Lyme disease

Recent animal bites → Tick borne encephalitis or Rabies.Recent animal bites → Tick borne encephalitis or Rabies. OccupationOccupation

• Forest worker, exposed to tick bitesForest worker, exposed to tick bites• Medical personnel, possible exposure to infectious diseases. Medical personnel, possible exposure to infectious diseases.

History contHistory cont.. SeasonSeason

• Japanese encephalitis is more common during the rainy season.Japanese encephalitis is more common during the rainy season.• Arbovirus infections are more frequent during summer and fall.Arbovirus infections are more frequent during summer and fall.

Predisposing factors:Predisposing factors:• Immunosuppression caused by disease and/or drug treatment. Immunosuppression caused by disease and/or drug treatment. • Organ transplant → Opportunistic infectionsOrgan transplant → Opportunistic infections• HIV → CNS infectionsHIV → CNS infections• HSV-2 encephalitis and Cytomegalovirus infection (CMV)HSV-2 encephalitis and Cytomegalovirus infection (CMV)

Drug ingestion and/or abuse Drug ingestion and/or abuse

TraumaTrauma

Initial SignsInitial Signs

HeadacheHeadache Malaise Malaise Anorexia Anorexia Nausea and VomitingNausea and Vomiting Abdominal painAbdominal pain

Developing SignsDeveloping Signs Altered LOC – mild lethargy to deep coma.Altered LOC – mild lethargy to deep coma. AMS – confused, delirious, disoriented.AMS – confused, delirious, disoriented. Mental aberrations: Mental aberrations:

• hallucinationshallucinations• agitationagitation• personality change personality change • behavioral disorders behavioral disorders • occasionally frank psychosisoccasionally frank psychosis

Focal or general seizures in >50% severe Focal or general seizures in >50% severe cases.cases.

Severe focused neurologic deficits.Severe focused neurologic deficits.

Neurologic SignsNeurologic Signs Virtually every possible focal neurological Virtually every possible focal neurological

disturbance has been reported.disturbance has been reported. Most CommonMost Common

• AphasiaAphasia• Ataxia Ataxia • Hemiparesis.Hemiparesis.• Involuntary movementsInvoluntary movements• Cranial nerve deficits (ocular palsies, facial Cranial nerve deficits (ocular palsies, facial

weakness)weakness)

Other Causes of Other Causes of EncephalopathyEncephalopathy

Anoxic/Ischemic conditionsAnoxic/Ischemic conditions Metabolic disordersMetabolic disorders Nutritional deficiencyNutritional deficiency Toxic (Accidental & Intentional)Toxic (Accidental & Intentional) Systemic infectionsSystemic infections Critical illnessCritical illness Malignant hypertensionMalignant hypertension Mitochondrial cytopathy (Reye’s and MELAS Mitochondrial cytopathy (Reye’s and MELAS

syndromes)syndromes) Hashimoto’s encephalopathyHashimoto’s encephalopathy Traumatic brain injuryTraumatic brain injury Epileptic (non-convulsive status)Epileptic (non-convulsive status) CJD (Mad Cow)CJD (Mad Cow)

Differential DiagnosisDifferential Diagnosis

Distinguish EtiologyDistinguish Etiology

• (1) Bacterial infection and other infectious conditions(1) Bacterial infection and other infectious conditions• (2) Parameningeal infections or partially treated bacterial (2) Parameningeal infections or partially treated bacterial

meningitismeningitis• (3) Nonviral infectious meningitides where cultures may be (3) Nonviral infectious meningitides where cultures may be

negative (e.g., fungal, tuberculous, parasitic, or syphilitic negative (e.g., fungal, tuberculous, parasitic, or syphilitic disease)disease)

• (4) Meningitis secondary to noninfectious inflammatory (4) Meningitis secondary to noninfectious inflammatory diseasesdiseases

VIRAL ENCEPHALITISVIRAL ENCEPHALITIS

DIAGNOSIS. DIAGNOSIS. LP:LP:

CSF usually colorlessCSF usually colorless-- slightly slightly pressure pressure-- initially a neutrophilic pleocytosis, which rapidly initially a neutrophilic pleocytosis, which rapidly converts to lymphocytesconverts to lymphocytes-- proteins are proteins are -- glucose is normal glucose is normal

PCR for HSE and other viral infection is diagnostic .PCR for HSE and other viral infection is diagnostic .

VIRAL ENCEPHALITISVIRAL ENCEPHALITIS

DIAGNOSISDIAGNOSIS..MRIMRI::

May show temporal or orbitofrontal cortex enhancement or May show temporal or orbitofrontal cortex enhancement or edema in HSE.edema in HSE.

In most other acute viral encephalities , neuroimaging In most other acute viral encephalities , neuroimaging finding are nonspecific.finding are nonspecific.

Can exclude subdural bleeds, tumor, and sinus thrombosis.Can exclude subdural bleeds, tumor, and sinus thrombosis.EEG:EEG:

• Non specific Non specific • Diffuse slowing .Diffuse slowing .• Focal abnormalities in the temporal region . HSVFocal abnormalities in the temporal region . HSV

Brain biopsy :Brain biopsy : Reserved for patients who are worsening, have an Reserved for patients who are worsening, have an

undiagnosed lesion after scan, or a poor response to undiagnosed lesion after scan, or a poor response to acyclovir.acyclovir.

TreatmentTreatment.. Only HSV disease has specific therapy available. Acyclovir is capable

of improving patient outcome.

dose : 10 mg/kg intravenously every 8 hours. Duration 14-21 days.

• ganciclovir can be used in CMV infections.• pleconaril has shown promise in enteroviral.

Outcomes Outcomes are variable depending on etiology.

EEE and St. Louis encephalitis generally have high mortality rates and Severe neurologic sequelae among survivors.

WNV is associated with significant morbidity and morality.

Mortality of HSV encephalitis before acyclovir was 60% to 70%, and with treatment approximately 30%.

Cognitive disability,seizures, and motor deficits are common sequelae seen among survivors

Bacterial and NonBacterial and Non--Bacterial CNS Bacterial CNS InfectionsInfections

EMERGENCY NEUROLOGY LECTURE EMERGENCY NEUROLOGY LECTURE SERIES SERIES

  

JULY 7, 2010JULY 7, 2010

DrDr. . Abdullah AlAbdullah Al--Salti R3Salti R3