Meningitis and Encephalitis in the Older Patient

Meningitis and Meningitis and Encephalitis in the Encephalitis in the Older PatientOlder Patient

Debra Bynum, MDDebra Bynum, MDDivision of Geriatric MedicineDivision of Geriatric MedicineUniversity of North Carolina Chapel HillUniversity of North Carolina Chapel Hill

April 2007

OutlineOutline Cases for thought…Cases for thought… Meningitis and Encephalitis: general features Meningitis and Encephalitis: general features

and causesand causes Diagnosis: review of CSF findingsDiagnosis: review of CSF findings Meningitis: specific causesMeningitis: specific causes Encephalitis: specific causesEncephalitis: specific causes Zoom in on important arboviruses and tick-Zoom in on important arboviruses and tick-

borne illnessesborne illnesses Summary of diagnosis and treatmentSummary of diagnosis and treatment Review of the casesReview of the cases

CasesCases 1. Active 78-y/o man with prior hx of aortic valve 1. Active 78-y/o man with prior hx of aortic valve

replacement years ago, presents with fever, slight replacement years ago, presents with fever, slight confusion, dehydration. Initial concern for SBE, but confusion, dehydration. Initial concern for SBE, but CSF :TNC of 20. His serum Na 128. All cultures negative. CSF :TNC of 20. His serum Na 128. All cultures negative. What would the DDX include?What would the DDX include?

2. 85-y/o with severe dementia admitted with fever, ?stiff 2. 85-y/o with severe dementia admitted with fever, ?stiff neck and worsening confusion and lethargy. CXR and U/A neck and worsening confusion and lethargy. CXR and U/A are negative. What would you do?are negative. What would you do?

3. Healthy community living 75-y/o presents with 3. Healthy community living 75-y/o presents with personality changes, confusion, agitation. She has no fever, personality changes, confusion, agitation. She has no fever, no other evidence of infection. What to do?no other evidence of infection. What to do?

4. 80-year-old man presents with low grade fever and coma 4. 80-year-old man presents with low grade fever and coma after several days of myalgias and viral-like illness. Exam is after several days of myalgias and viral-like illness. Exam is notable for some Parkinsonian type features… initial notable for some Parkinsonian type features… initial concern would be for ?concern would be for ?

MeningitisMeningitis Inflammation of the meninges Inflammation of the meninges Classic triad:Classic triad:

FeverFever HeadacheHeadache

Severe, frontal, photophobia, n/vSevere, frontal, photophobia, n/v Jolt accentuationJolt accentuation

Meningismus/altered mental status Meningismus/altered mental status

Meningeal signsMeningeal signs Kernig sign: one leg with hip flexed, pain in back Kernig sign: one leg with hip flexed, pain in back

with extension of kneewith extension of knee Brudzinski sign: flexion of legs and thighs when Brudzinski sign: flexion of legs and thighs when

neck is flexedneck is flexed

EncephalitisEncephalitis

Inflammation of the cerebral cortexInflammation of the cerebral cortex Fever, HA, altered mental statusFever, HA, altered mental status Key: early mental status changesKey: early mental status changes More commonly virusesMore commonly viruses Obtundation/comaObtundation/coma Behavioral or speech problems, neurological Behavioral or speech problems, neurological

signs, seizuressigns, seizures MeningoencephalitisMeningoencephalitis Difference from meningitis: less likely fever, Difference from meningitis: less likely fever,

more likely personality/behavioral changesmore likely personality/behavioral changes

Causes of MeningitisCauses of Meningitis

BacterialBacterial ViralViral Fungal: cryptococcusFungal: cryptococcus Mycobacteria: MTBMycobacteria: MTB Parasitic/protozoa: Naegleria fowleriParasitic/protozoa: Naegleria fowleri NoninfectiousNoninfectious

MedicationsMedications ParaneoplasticParaneoplastic

Acute Bacterial Acute Bacterial MeningitisMeningitis

Streptococcus pneumoniaeStreptococcus pneumoniae Neisseria meningitidisNeisseria meningitidis Listeria monocytogenesListeria monocytogenes Haemophilus influenzae: nearly Haemophilus influenzae: nearly

unheard of since vaccinationsunheard of since vaccinations Less common: Gram negatives Less common: Gram negatives

(Klebsiella, E. coli)(Klebsiella, E. coli) History of procedure: StaphylococcusHistory of procedure: Staphylococcus

Viral MeningitisViral Meningitis Aseptic meningitisAseptic meningitis Spectrum with encephalitis, meningo-Spectrum with encephalitis, meningo-

enchephalitisenchephalitis EnterovirusesEnteroviruses HSV HSV VZVVZV Arboviruses (arthropod borne viruses)Arboviruses (arthropod borne viruses)

West Nile, Eastern Equine, Western Equine, West Nile, Eastern Equine, Western Equine, St. Louis, California, Japanese EncephalitisSt. Louis, California, Japanese Encephalitis

HIVHIV Rabies virusRabies virus AdenovirusAdenovirus CMV, EBVCMV, EBV

EncephalitisEncephalitis ViralViral

HSVHSV ArbovirusesArboviruses VZV, CMV, EBV, HIV, rabiesVZV, CMV, EBV, HIV, rabies EnterovirusesEnteroviruses

BacterialBacterial Listeria monocytogenesListeria monocytogenes

Tick-borne illnessesTick-borne illnesses RMSF: Rickettsia rickettsiiRMSF: Rickettsia rickettsii STARI: Borrelia lonestariSTARI: Borrelia lonestari Lyme: Borrelia burgdorferiLyme: Borrelia burgdorferi Ehrlichiosis: Ehrlichia chaffoensisEhrlichiosis: Ehrlichia chaffoensis

Meningitis in the ElderlyMeningitis in the Elderly

Decreased total incidence; increased in elderlyDecreased total incidence; increased in elderly Increased prevalence of Listeria (25%)Increased prevalence of Listeria (25%) 30-50%: S. pneumoniae30-50%: S. pneumoniae Less likely Neisseria and HaemophilusLess likely Neisseria and Haemophilus Less likely fever and meningeal signs; more Less likely fever and meningeal signs; more

likely neurological symptoms, seizure, comalikely neurological symptoms, seizure, coma More often complicated by pneumoniaMore often complicated by pneumonia Older patients with neurological impairment: Older patients with neurological impairment:

50% mortality50% mortality

MeningitisMeningitis Risk FactorsRisk Factors

Age (bimodal peak)Age (bimodal peak) Prior neurosurgery, alcoholism, malignancy, Prior neurosurgery, alcoholism, malignancy,

steroids, HIV, sinusitis, DMsteroids, HIV, sinusitis, DM

Clinical suspicionClinical suspicion Triad: fever, nuchal rigidity, altered mental Triad: fever, nuchal rigidity, altered mental

status: only seen in 40% elderly status: only seen in 40% elderly Only 59% of elderly patients with acute Only 59% of elderly patients with acute

bacterial meningitis had fever bacterial meningitis had fever Most have at least ONE symptomMost have at least ONE symptom

The DiagnosisThe Diagnosis

LP if suspicionLP if suspicion Do not delay antibiotics if suspected!Do not delay antibiotics if suspected! CT prior to LP in patients with focal neurological CT prior to LP in patients with focal neurological

deficits, seizures, HIV, or elderlydeficits, seizures, HIV, or elderly MRI: to identify areas of CNS involvementMRI: to identify areas of CNS involvement

Temporal involvement with HSVTemporal involvement with HSV Basilar meningitis with TBBasilar meningitis with TB

The Lumbar Puncture: The Lumbar Puncture: RisksRisks

Headache: 10-25%Headache: 10-25% Typical: appears suddenly upon standingTypical: appears suddenly upon standing Decrease CSF pressure with small leak Decrease CSF pressure with small leak Decrease risk: small (<20 g) needle, leave Decrease risk: small (<20 g) needle, leave

patient prone after procedurepatient prone after procedure Blood patchBlood patch

Infection (small)Infection (small) Local bleeding: traumatic tap to epidural Local bleeding: traumatic tap to epidural

hematomahematoma Brain herniationBrain herniation

The LPThe LP Opening PressureOpening Pressure

Important dataImportant data Only in lateral decubitus (not position usually Only in lateral decubitus (not position usually

done under radiology)done under radiology)

XanthochromiaXanthochromia Yellow/orange color of centrifuged CSFYellow/orange color of centrifuged CSF RBC lysis – oxyhemoglobin, bilirubinRBC lysis – oxyhemoglobin, bilirubin Blood in subarachnoid space at least 2-4 hrsBlood in subarachnoid space at least 2-4 hrs More likely due to blood in CSF and less likely More likely due to blood in CSF and less likely

traumatic taptraumatic tap

CSF FindingsCSF FindingsNormalNormal BacteriBacteri

alalViralViral FungalFungal TBTB otherother

WBCWBC

(TNC)(TNC)0-50-5 100-100-

10,00010,0005-30005-3000 5-5005-500 5-5005-500 paraneoparaneo

Cell Cell typetype

>50% >50% PMNPMN

>50% >50% lymphslymphs



MonocloMonoclonal, nal, atypiaatypia

ProteinProtein 50-80 50-80 mg/dLmg/dL

>200>200 Nl/slight Nl/slight increaseincrease

Nl/slight Nl/slight increaseincrease

IncreaseIncrease increaseincreasedd

GlucoseGlucose 70-80 70-80 mg/dLmg/dL

>60% >60% serum serum

<40, <40, <60% of <60% of serum serum glucoseglucose

NormalNormal normalnormal <40 or <40 or nlnl

decreasdecreasee

Gm Gm stainstain

60% +60% + NegNeg 50% 50% india ink india ink + crypto+ crypto

AFB + AFB + 25-35%25-35%

PressurPressuree

75-200 75-200 mm Hgmm Hg

IncInc NlNl IncInc Nl/incNl/inc

CSF: Some CatchesCSF: Some Catches

Protein least specificProtein least specific TB: early neutrophilic predominanceTB: early neutrophilic predominance Encephalitis, RMSF, tick-borne illnesses: inc CSF Encephalitis, RMSF, tick-borne illnesses: inc CSF

WBCWBC Listeria: misread as “contamination”/diphtheroidsListeria: misread as “contamination”/diphtheroids Listeria: bacterial meningitis that can have Listeria: bacterial meningitis that can have

significant encephalitis and abscess, and CSF with significant encephalitis and abscess, and CSF with lymphocytes!lymphocytes!

RBCs that do not clear: SAH or HSVRBCs that do not clear: SAH or HSV

CSF: More PearlsCSF: More Pearls

Correction factors for traumatic tapCorrection factors for traumatic tap

““trauma” and RBCs increase protein and with trauma” and RBCs increase protein and with an increase in RBCs come an increase in an increase in RBCs come an increase in WBCsWBCs

True CSF protein = subtract 1 mg/dL protein True CSF protein = subtract 1 mg/dL protein for every 1000 RBC/mm3for every 1000 RBC/mm3

True WBC in CSF: actual WBC in CSF – (WBC True WBC in CSF: actual WBC in CSF – (WBC in blood x RBC in CSF)/ RBC in bloodin blood x RBC in CSF)/ RBC in blood

Meningitis: Specific Meningitis: Specific CausesCauses

Strep Pneumoniae Strep Pneumoniae MeningitisMeningitis

Now most common cause (H flu rare)Now most common cause (H flu rare) 30-50% cases of bacterial meningitis in elderly30-50% cases of bacterial meningitis in elderly Otitis 30%, sinusitis 8%, pneumonia 18%Otitis 30%, sinusitis 8%, pneumonia 18% Elderly more often have pneumonia (bad)Elderly more often have pneumonia (bad) Bad markers: older age, low platelets, dec CSF Bad markers: older age, low platelets, dec CSF

glucose, no otogenic focusglucose, no otogenic focus Vaccination: recommended in all over age 65Vaccination: recommended in all over age 65

Efficacy in elderly/immunocompromised NOT Efficacy in elderly/immunocompromised NOT clearclear

Decrease bacteremia/meningitisDecrease bacteremia/meningitis

ListeriaListeria

Food-borne outbreaksFood-borne outbreaks Herd animalsHerd animals Common, likely cause of mild GI illnesses Common, likely cause of mild GI illnesses Invasive disease with bacteremia and CNS Invasive disease with bacteremia and CNS

involvement may follow other GI infection involvement may follow other GI infection (piggy back…)(piggy back…)

Increased risk with depressed cellular Increased risk with depressed cellular immunity: pregnant women, elderly, AIDS, immunity: pregnant women, elderly, AIDS, lymphoma, steroid use, transplant patientslymphoma, steroid use, transplant patients

Listeria…Listeria…

Small, anaerobic gm + baccillusSmall, anaerobic gm + baccillus Look like diphtheroids, contaminants Look like diphtheroids, contaminants Cerebritis, brain abscessCerebritis, brain abscess Confusion, altered LOC, seizure, movementConfusion, altered LOC, seizure, movement Mortality 22% in older patients with CNS dzMortality 22% in older patients with CNS dz 20% of all cases of bacterial meningitis in 20% of all cases of bacterial meningitis in

patients over age 60patients over age 60 Brain abscess: 10% CNS infectionsBrain abscess: 10% CNS infections

Usually due to bacteremiaUsually due to bacteremia Concomitant meningitis in 25-40% (rare with Concomitant meningitis in 25-40% (rare with

other causes of brain abscess)other causes of brain abscess)

Listeria… Big PointsListeria… Big Points

NOT uncommon in elderlyNOT uncommon in elderly Meningitis, encephalitis, focal brain abscessMeningitis, encephalitis, focal brain abscess Add AmpicillinAdd Ampicillin Diphtheroids in CSF: listeria unless proven Diphtheroids in CSF: listeria unless proven

otherwiseotherwise

TB MeningitisTB Meningitis Tuberculous meningitis (most common)Tuberculous meningitis (most common) Intracranial tuberculomasIntracranial tuberculomas Spinal tuberculous arachnoiditisSpinal tuberculous arachnoiditis

Meningitis: inflammation from rupture of subependymal Meningitis: inflammation from rupture of subependymal tubercle into subarachnoid spacetubercle into subarachnoid space

Basilar meningitis, CN palsies, hydrocephalusBasilar meningitis, CN palsies, hydrocephalus

Subacute or chronicSubacute or chronic

Initial neutrophilic pattern on CSFInitial neutrophilic pattern on CSF

Very high CSF protein may be seenVery high CSF protein may be seen

AFB smears often neg; need HIGH volume sent to labAFB smears often neg; need HIGH volume sent to lab

Viral MeningitisViral Meningitis

Aseptic meningitisAseptic meningitis May be difficult to initially separate from May be difficult to initially separate from

partially treated bacterial meningitis (obligates partially treated bacterial meningitis (obligates empiric treatment for bacterial)empiric treatment for bacterial)

Differentiate from true aseptic (drug related Differentiate from true aseptic (drug related such as NSAIDs, paraneoplastic)such as NSAIDs, paraneoplastic)


Finland study: etiology found in 66% patients Finland study: etiology found in 66% patients with aseptic meningitiswith aseptic meningitis

Viral encephalitis: etiology only found in 36% Viral encephalitis: etiology only found in 36% casescases

Viral prodrome, sore throat, myalgias, ill Viral prodrome, sore throat, myalgias, ill contacts, GI complaints; summer/fall seasoncontacts, GI complaints; summer/fall season

Most common= enteroviruses (25%)Most common= enteroviruses (25%) EchovirusesEchoviruses CoxsackievirusCoxsackievirus


Less common causesLess common causes Adenoviruses: URI sxs, year roundAdenoviruses: URI sxs, year round CMV, EBV, HIV, influenzaeCMV, EBV, HIV, influenzae Measles, mumps, rabies, rubella, Measles, mumps, rabies, rubella,

varicellavaricella ?future avian flu (usually not CNS sxs, ?future avian flu (usually not CNS sxs,

more URI/pneumonia/ARDS and DIC)more URI/pneumonia/ARDS and DIC)

Encephalitis: Specific Encephalitis: Specific CausesCauses

Encephalitis Encephalitis Lethargica…Lethargica…

The Awakenings…The Awakenings… 1916: von Economo described CNS disorder 1916: von Economo described CNS disorder

with lethargy and Parkinsonian features with lethargy and Parkinsonian features following viral syndrome with pharyngitisfollowing viral syndrome with pharyngitis

1916-1927 epidemic; now sporadic cases1916-1927 epidemic; now sporadic cases 1918: influenza pandemic, ?connection (?1918: influenza pandemic, ?connection (?

immune mediated process)immune mediated process)


More likely to be viralMore likely to be viral Etiology only found in 35% casesEtiology only found in 35% cases

HSV-1: 10% cases (but accounts for over HSV-1: 10% cases (but accounts for over 50% cases in patients over 50)50% cases in patients over 50)

HSV-2HSV-2 VZV (?up to 10% in some series)VZV (?up to 10% in some series) Tick or insect borne diseases: 10%Tick or insect borne diseases: 10%


Acute Viral EncephalitisAcute Viral Encephalitis Direct viral infection of neuronal cellsDirect viral infection of neuronal cells Perivascular inflammationPerivascular inflammation Destruction of gray matterDestruction of gray matter

Post-Infectious EncephalomyelitisPost-Infectious Encephalomyelitis Follows viral or bacterial infectionFollows viral or bacterial infection Demyelination of white matterDemyelination of white matter ?autoimmune component triggered by ?autoimmune component triggered by

infectious agentinfectious agent

HSV EncephalitisHSV Encephalitis

2-4 cases/million people/year2-4 cases/million people/year Acute infection or more commonly reactivation Acute infection or more commonly reactivation

of latent infection (trigeminal nerve ganglion)of latent infection (trigeminal nerve ganglion) Characteristic site of damage: temporal lobeCharacteristic site of damage: temporal lobe

MRI findings of necrosis in temporal lobeMRI findings of necrosis in temporal lobe Necrosis = RBC s on CSF! Necrosis = RBC s on CSF!

HSV EncephalitisHSV Encephalitis

Dysphasia, bizarre behavior, seizuresDysphasia, bizarre behavior, seizures Abnormal EEGAbnormal EEG High mortality: 30% with treatmentHigh mortality: 30% with treatment Survivors: 10% long term disabilitySurvivors: 10% long term disability Fever +/-Fever +/- Treatment: Acyclovir (60-75% mortality without Treatment: Acyclovir (60-75% mortality without

treatment)treatment)

HSV Encephalitis: Big HSV Encephalitis: Big PointsPoints

Odd behavior, think encephalitisOdd behavior, think encephalitis If thinking encephalitis, add acyclovirIf thinking encephalitis, add acyclovir RBCs on CSF (with xanthochromia or lack of RBCs on CSF (with xanthochromia or lack of

clearing between tube 1 and 4), think HSVclearing between tube 1 and 4), think HSV Temporal symptomsTemporal symptoms Temporal necrosis or abnormalities on MRITemporal necrosis or abnormalities on MRI

Arboviruses and Arboviruses and EncephalitisEncephalitis

Arbovirus: Arthropod Borne VirusArbovirus: Arthropod Borne Virus RNA viruses transmitted by mosquitoes or ticksRNA viruses transmitted by mosquitoes or ticks 10 % cases of sporadic encephalitis (?higher in 10 % cases of sporadic encephalitis (?higher in

elderly, up to 50% cases during epidemics)elderly, up to 50% cases during epidemics)

Arboviruses and Arboviruses and EncephalitisEncephalitis

Alphavirus family:Alphavirus family: Eastern Equine Encephalitis **Eastern Equine Encephalitis ** Western Equine EncephalitisWestern Equine Encephalitis

Flavivirus family:Flavivirus family: St Louis Encephalitis **St Louis Encephalitis ** Japanese EncephalitisJapanese Encephalitis California EncephalitisCalifornia Encephalitis West Nile Virus **West Nile Virus **

West Nile Virus and West Nile Virus and Encephalitis in the ElderlyEncephalitis in the Elderly

West Nile VirusWest Nile Virus

19371937: West Nile district Uganda (mild cases): West Nile district Uganda (mild cases) Middle east/ Israel (14% fatality)Middle east/ Israel (14% fatality) 19961996: outbreak in Romania (4% fatality): outbreak in Romania (4% fatality) 19991999: NY outbreak (11% fatality): NY outbreak (11% fatality) Subsequent west spread to most statesSubsequent west spread to most states 20022002: 4156 reported cases in US, 284 deaths: 4156 reported cases in US, 284 deaths 20032003: 9858 cases, 262 deaths: 9858 cases, 262 deaths


Season: summerSeason: summer Mosquito transmission (currently infects 43/ Mosquito transmission (currently infects 43/

174 different types of North American 174 different types of North American mosquitoes)mosquitoes)

Other routesOther routes PlacentaPlacenta LactationLactation TransfusionTransfusion Organ transplantOrgan transplant


Disease of the elderlyDisease of the elderly Higher mortality in elderlyHigher mortality in elderly Other risk factors not clear (?maybe HTN and Other risk factors not clear (?maybe HTN and

DM leading to better virus entry)DM leading to better virus entry)

WNV: PredictorsWNV: Predictors Admission diagnoses:Admission diagnoses:

30%: aseptic meningitis30%: aseptic meningitis 15%: fever15%: fever 18%: viral infection18%: viral infection 14%: UTI14%: UTI 10% pneumonia10% pneumonia 7% : encephalitis7% : encephalitis 5%: probable WNV (year 2001)5%: probable WNV (year 2001)

Mortality rates highest with:Mortality rates highest with: Initial diagnosis of encephalitis (35% of those who Initial diagnosis of encephalitis (35% of those who

died), died), No headache (50% had HA, 7% those that died had No headache (50% had HA, 7% those that died had

HA), andHA), and Initial mental status changesInitial mental status changes

WNVWNV

Presenting symptomsPresenting symptoms HA, fever, mental status changesHA, fever, mental status changes CN findings, optic neuritisCN findings, optic neuritis MyoclonusMyoclonus

Flaccid ParalysisFlaccid Paralysis With or without encephalitisWith or without encephalitis Asymmetric weakness/paralysis, no sensory Asymmetric weakness/paralysis, no sensory

lossloss Anterior horn cells (polio like)Anterior horn cells (polio like) Absent DTRsAbsent DTRs

WNVWNV

Movement DisordersMovement Disorders ParkinsonianParkinsonian TremorsTremors BradykinesiaBradykinesia Cogwheel rigidityCogwheel rigidity Postural instabilityPostural instability Masked faciesMasked facies 80-100% will have rest or intention 80-100% will have rest or intention

tremor tremor 30% will have myoclonus30% will have myoclonus

WNV: DiagnosisWNV: Diagnosis

High index of suspicionHigh index of suspicion CSF: usually 200 TNC; 5-10% can have over 500 CSF: usually 200 TNC; 5-10% can have over 500

TNC, 5% with < 5 TNCTNC, 5% with < 5 TNC CSF with 50% neutrophilsCSF with 50% neutrophils Elevated CSF proteinElevated CSF protein CSF for ab studies: anti WNV ab, and negative CSF for ab studies: anti WNV ab, and negative

SLE IgM (up to 40% cross reactivity in earlier SLE IgM (up to 40% cross reactivity in earlier studies)studies)

WNV: TreatmentWNV: Treatment

?nucleoside analogues (ribavirin – no benefit in ?nucleoside analogues (ribavirin – no benefit in Israel)Israel)

Human Immunoglobulin : protective antibodies Human Immunoglobulin : protective antibodies (patients from Israel with high titers of anti-(patients from Israel with high titers of anti-WNV ab); if effective, only in early diseaseWNV ab); if effective, only in early disease

?vaccine development (effective in horses in ?vaccine development (effective in horses in 2001)2001)

?inactivated JEV vaccine??inactivated JEV vaccine?

Meningitis and Meningitis and Encephalitis: OthersEncephalitis: Others

Tick-Borne DiseasesTick-Borne Diseases

RMSF **RMSF ** Lyme Disease **Lyme Disease ** Ehrlichiosis **Ehrlichiosis ** STARI **STARI ** TularemiaTularemia BabesiosisBabesiosis Colorado Tick FeverColorado Tick Fever

Rocky Mountain Spotted Rocky Mountain Spotted FeverFever

Rickettsia rickettsiiRickettsia rickettsii Gm negative intracellular bacteriaGm negative intracellular bacteria Endothelial cells: small vessel vasculitisEndothelial cells: small vessel vasculitis

Southeast, summerSoutheast, summer Dog Tick, Wood TickDog Tick, Wood Tick 22ndnd most common tick-borne illness most common tick-borne illness

Fever/headache/nausea/rashFever/headache/nausea/rash 80% 80% Rash:Rash: blanching maculopapular, palms/soles, blanching maculopapular, palms/soles,

spreads centrally, later petechial and spreads centrally, later petechial and purpuricpurpuric

Hyponatremia, thrombocytopenia, inc ALTHyponatremia, thrombocytopenia, inc ALT CSFCSF: inc TNC, inc protein; neg gram stain: inc TNC, inc protein; neg gram stain

RMSF: DiagnosisRMSF: Diagnosis

Clinical suspicionClinical suspicion Low threshold to empirically treatLow threshold to empirically treat Rash may be absent in 20% Rash may be absent in 20% RMSF serologies: initial may be negative; need RMSF serologies: initial may be negative; need

convalescent titers several weeks laterconvalescent titers several weeks later

RMSF: TreatmentRMSF: Treatment

Doxycycline 100 BIDDoxycycline 100 BID Do not delay Do not delay ?newer quinolones: probably, but no studies ?newer quinolones: probably, but no studies

and no recommendationsand no recommendations No indication for prophylactic treatment after No indication for prophylactic treatment after

uncomplicated tick biteuncomplicated tick bite Prevention: frequent inspection Prevention: frequent inspection

RMSF: Big PointsRMSF: Big Points

Empiric Treatment if even suspectedEmpiric Treatment if even suspected In North Carolina, any fever, HA, neuro In North Carolina, any fever, HA, neuro

syndrome will need treatmentsyndrome will need treatment First serology titers NOT reliableFirst serology titers NOT reliable Hyponatremia, low platelets, elevated LFTs, Hyponatremia, low platelets, elevated LFTs,

think RMSF…think RMSF… Do not wait for the rash…Do not wait for the rash…

Lyme DiseaseLyme Disease

Borrelia burgdorferiBorrelia burgdorferi Deer Tick (smaller)Deer Tick (smaller) NE/Great Lakes, but reported in almost allNE/Great Lakes, but reported in almost all

StagesStages 1: erythema migrans rash, viral-like 1: erythema migrans rash, viral-like

syndromesyndrome 2. early disseminated phase, secondary 2. early disseminated phase, secondary

cutaneous cutaneous 3. late/chronic: arthritis, cns involvement (CN 3. late/chronic: arthritis, cns involvement (CN

palsies), myocardial damagepalsies), myocardial damage

STARISTARI

Southern Tick Associated Rash IllnessSouthern Tick Associated Rash Illness Lyme-like infection in North Carolina with Lyme-like infection in North Carolina with

negative Lyme serologiesnegative Lyme serologies Lone Star TickLone Star Tick Borrelia lonestariBorrelia lonestari

EhrlichiaEhrlichia

““Rashless” RMSFRashless” RMSF Fever, headacheFever, headache CSF: pleocytosis, neg gm stain, inc proteinCSF: pleocytosis, neg gm stain, inc protein

Hyponatremia, thrombocytopenia, elevated LFTsHyponatremia, thrombocytopenia, elevated LFTs Lone Star tick, Dog TickLone Star tick, Dog Tick Same treatment as RMSFSame treatment as RMSF Serologies and convalescent titersSerologies and convalescent titers

Overall Picture: Overall Picture: DiagnosisDiagnosis

Difficult to initially separate meningitis from Difficult to initially separate meningitis from encephalitis in elderly;encephalitis in elderly; both present with mental both present with mental status changes; elderly with meningitis less likely status changes; elderly with meningitis less likely to have feverto have fever

Other infections cause Other infections cause deliriumdelirium in elderly in elderly Red flagsRed flags

Any CNS focalityAny CNS focality Behavioral changes/personality changesBehavioral changes/personality changes SeizuresSeizures Lack of other source of infectionLack of other source of infection Headache, ? nuchal rigidity, ill contactsHeadache, ? nuchal rigidity, ill contacts Season, outdoor activitySeason, outdoor activity Low threshold to do LP Low threshold to do LP

Overall PictureOverall Picture

Main PlayersMain Players Strep pneumoniaeStrep pneumoniae ListeriaListeria Viral agents such as enterovirusesViral agents such as enteroviruses HSVHSV Arboviruses (including WNV now)Arboviruses (including WNV now) Tick-borne bacteria (RMSF, ehrilchia, STARI)Tick-borne bacteria (RMSF, ehrilchia, STARI)

If things are not adding If things are not adding up…up…

Less common causesLess common causes VZVVZV Rabies virusRabies virus Post-measles, mumps, cmv, ebvPost-measles, mumps, cmv, ebv AdenovirusesAdenoviruses TBTB ProtozoaProtozoa CryptococcusCryptococcus Gm negatives: klebsiella, e coliGm negatives: klebsiella, e coli

DiagnosisDiagnosis

CSFCSF Elevated protein least specificElevated protein least specific Acute bacterial meningitis usually has high TNC, low Acute bacterial meningitis usually has high TNC, low

glu, unless partially treated or listeriaglu, unless partially treated or listeria More than 2-3 TNC is not normalMore than 2-3 TNC is not normal Gram stain, culture, PCR for HSV, viral studies for Gram stain, culture, PCR for HSV, viral studies for

enteroviruses, serologies for arbovirusesenteroviruses, serologies for arboviruses Latex agglutination studies: NOT helpfulLatex agglutination studies: NOT helpful Serum for RMSF/ehrlichiosis titers: initial and Serum for RMSF/ehrlichiosis titers: initial and

convalescent titersconvalescent titers

TreatmentTreatment

Initial empiric treatmentInitial empiric treatment OK to shotgun pending culture and test results OK to shotgun pending culture and test results

the first 24 - 48 hours!the first 24 - 48 hours! Risk of s. pneumoniae resistance and high Risk of s. pneumoniae resistance and high

mortality of untreated disease – vancomycin mortality of untreated disease – vancomycin initiallyinitially

Treatment: Treatment: DexamethasoneDexamethasone

Acute bacterial meningitisAcute bacterial meningitis Decreased mortality/morbidity (20 min prior to Decreased mortality/morbidity (20 min prior to

abx)abx) Recommended: proven S. pneumoniae, high Recommended: proven S. pneumoniae, high

opening pressure, pos gm stainopening pressure, pos gm stain Not clear with other causes, subgroups like elderlyNot clear with other causes, subgroups like elderly Probably not bad effects with viral causesProbably not bad effects with viral causes Dose: .4 mg/kg Q 6 hrs for 2-4 daysDose: .4 mg/kg Q 6 hrs for 2-4 days ?decrease vancomycin crossing blood-brain barrier?decrease vancomycin crossing blood-brain barrier

Treatment SummaryTreatment Summary

VancomycinVancomycin Ceftriaxone/cefotaximeCeftriaxone/cefotaxime Ampicillin Ampicillin AcyclovirAcyclovir DoxycyclineDoxycycline ?dexamethasone?dexamethasone OK to cover for all for first 24-48 hours, then OK to cover for all for first 24-48 hours, then

narrow based upon CSF results and serologiesnarrow based upon CSF results and serologies

CASESCASES

1. Active 78-y/o man with prior hx of aortic 1. Active 78-y/o man with prior hx of aortic valve replacement years ago, presents with valve replacement years ago, presents with fever, slight confusion, dehydration. fever, slight confusion, dehydration.

Initial concern for SBE, but CSF :TNC of 20. Initial concern for SBE, but CSF :TNC of 20. His serum Na 128. All cultures negative. His serum Na 128. All cultures negative. What would the DDX include?What would the DDX include?

CASESCASES

2. 85-y/o with severe dementia admitted with 2. 85-y/o with severe dementia admitted with fever, ?stiff neck and worsening confusion and fever, ?stiff neck and worsening confusion and lethargy. lethargy.

CXR and U/A are negative. CXR and U/A are negative.

What would you do?What would you do?

CASESCASES

3. Healthy community living 75-y/o presents with 3. Healthy community living 75-y/o presents with personality changes, confusion, agitation.personality changes, confusion, agitation.

She has no fever, no other evidence of infection. She has no fever, no other evidence of infection.

What to do?What to do?

CASESCASES

4. 80-year-old man presents with low grade 4. 80-year-old man presents with low grade fever and coma after several days of myalgias fever and coma after several days of myalgias and viral like illness. and viral like illness.

Exam is notable for some Parkinsonian type Exam is notable for some Parkinsonian type features… features…

initial concern would be for ?initial concern would be for ?

Documents

Meningitis and Encephalitis in the Older Patient