Meningitis and Encephalitis in t

							Meningitis and
Encephalitis in the Older
Patient

Debra Bynum, MD
Division of Geriatric Medicine
University of North Carolina Chapel Hill




                           April 2007
                     Outline
   Cases for thought…
   Meningitis and Encephalitis: general features and
    causes
   Diagnosis: review of CSF findings
   Meningitis: specific causes
   Encephalitis: specific causes
   Zoom in on important arboviruses and tick-borne
    illnesses
   Summary of diagnosis and treatment
   Review of the cases
                       Cases
   1. Active 78-y/o man with prior hx of aortic valve
    replacement years ago, presents with fever, slight
    confusion, dehydration. Initial concern for SBE, but
    CSF :TNC of 20. His serum Na 128. All cultures
    negative. What would the DDX include?

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

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

   4. 80-year-old man presents with low grade fever and
    coma after several days of myalgias and viral-like
    illness. Exam is notable for some Parkinsonian type
    features… initial concern would be for ?
                    Meningitis
   Inflammation of the meninges
   Classic triad:
       Fever
       Headache
          Severe, frontal, photophobia, n/v
          Jolt accentuation
       Meningismus/altered mental status

   Meningeal signs
       Kernig sign: one leg with hip flexed, pain in back
        with extension of knee
       Brudzinski sign: flexion of legs and thighs when
        neck is flexed
                  Encephalitis

   Inflammation of the cerebral cortex
   Fever, HA, altered mental status
   Key: early mental status changes
   More commonly viruses
   Obtundation/coma
   Behavioral or speech problems, neurological signs,
    seizures
   Meningoencephalitis
   Difference from meningitis: less likely fever, more
    likely personality/behavioral changes
        Causes of Meningitis
 Bacterial
 Viral
 Fungal: cryptococcus
 Mycobacteria: MTB
 Parasitic/protozoa: Naegleria fowleri
 Noninfectious
     Medications
     Paraneoplastic
 Acute Bacterial Meningitis
 Streptococcus pneumoniae
 Neisseria meningitidis
 Listeria monocytogenes
 Haemophilus influenzae: nearly unheard
  of since vaccinations
 Less common: Gram negatives
  (Klebsiella, E. coli)
 History of procedure: Staphylococcus
            Viral Meningitis
   Aseptic meningitis
   Spectrum with encephalitis, meningo-
    enchephalitis
   Enteroviruses
   HSV
   VZV
   Arboviruses (arthropod borne viruses)
      West Nile, Eastern Equine, Western Equine,
       St. Louis, California, Japanese Encephalitis
   HIV
   Rabies virus
   Adenovirus
   CMV, EBV
                  Encephalitis
   Viral
      HSV
      Arboviruses
      VZV, CMV, EBV, HIV, rabies
      Enteroviruses


   Bacterial
      Listeria monocytogenes


   Tick-borne illnesses
      RMSF: Rickettsia rickettsii
      STARI: Borrelia lonestari
      Lyme: Borrelia burgdorferi
      Ehrlichiosis: Ehrlichia chaffoensis
      Meningitis in the Elderly

   Decreased total incidence; increased in elderly
   Increased prevalence of Listeria (25%)
   30-50%: S. pneumoniae
   Less likely Neisseria and Haemophilus
   Less likely fever and meningeal signs; more likely
    neurological symptoms, seizure, coma
   More often complicated by pneumonia
   Older patients with neurological impairment: 50%
    mortality
                    Meningitis
   Risk Factors
      Age (bimodal peak)
      Prior neurosurgery, alcoholism, malignancy,
       steroids, HIV, sinusitis, DM

   Clinical suspicion
      Triad: fever, nuchal rigidity, altered mental status:
        only seen in 40% elderly
      Only 59% of elderly patients with acute bacterial
        meningitis had fever
      Most have at least ONE symptom
                The Diagnosis

   LP if suspicion
   Do not delay antibiotics if suspected!
   CT prior to LP in patients with focal neurological
    deficits, seizures, HIV, or elderly
   MRI: to identify areas of CNS involvement
      Temporal involvement with HSV
      Basilar meningitis with TB
    The Lumbar Puncture: Risks

   Headache: 10-25%
      Typical: appears suddenly upon standing
      Decrease CSF pressure with small leak
      Decrease risk: small (<20 g) needle, leave patient
       prone after procedure
      Blood patch
   Infection (small)
   Local bleeding: traumatic tap to epidural hematoma
   Brain herniation
                       The LP
   Opening Pressure
      Important data
      Only in lateral decubitus (not position usually done
       under radiology)

   Xanthochromia
      Yellow/orange color of centrifuged CSF
      RBC lysis – oxyhemoglobin, bilirubin
      Blood in subarachnoid space at least 2-4 hrs
      More likely due to blood in CSF and less likely
       traumatic tap
                     CSF Findings
            Normal   Bacterial Viral       Fungal      TB          other


WBC         0-5      100-      5-3000      5-500       5-500       paraneo
(TNC)                10,000
Cell type            >50%      >50%        >50%        >50%        Monoclon
                     PMN       lymphs      lymphs      lymphs      al, atypia
Protein     50-80    >200      Nl/slight   Nl/slight   Increase    increased
            mg/dL              increase    increase
Glucose     70-80    <40,      Normal      normal      <40 or nl   decrease
            mg/dL    <60% of
            >60%     serum
            serum    glucose
Gm stain             60% +     Neg         50%         AFB +
                                           india ink   25-35%
                                           + crypto
Pressure    75-200   Inc       Nl          Inc         Nl/inc
            mm Hg
          CSF: Some Catches

   Protein least specific
   TB: early neutrophilic predominance
   Encephalitis, RMSF, tick-borne illnesses: inc CSF WBC
   Listeria: misread as “contamination”/diphtheroids
   Listeria: bacterial meningitis that can have significant
    encephalitis and abscess, and CSF with lymphocytes!
   RBCs that do not clear: SAH or HSV
             CSF: More Pearls

   Correction factors for traumatic tap

       “trauma” and RBCs increase protein and with an
        increase in RBCs come an increase in WBCs
       True CSF protein = subtract 1 mg/dL protein for
        every 1000 RBC/mm3
       True WBC in CSF: actual WBC in CSF – (WBC in
        blood x RBC in CSF)/ RBC in blood
Meningitis: Specific Causes
Strep Pneumoniae Meningitis


   Now most common cause (H flu rare)
   30-50% cases of bacterial meningitis in elderly
   Otitis 30%, sinusitis 8%, pneumonia 18%
   Elderly more often have pneumonia (bad)
   Bad markers: older age, low platelets, dec CSF
    glucose, no otogenic focus
   Vaccination: recommended in all over age 65
      Efficacy in elderly/immunocompromised NOT clear
      Decrease bacteremia/meningitis
                     Listeria

   Food-borne outbreaks
   Herd animals
   Common, likely cause of mild GI illnesses
   Invasive disease with bacteremia and CNS
    involvement may follow other GI infection (piggy
    back…)
   Increased risk with depressed cellular immunity:
    pregnant women, elderly, AIDS, lymphoma, steroid
    use, transplant patients
                   Listeria…

   Small, anaerobic gm + baccillus
   Look like diphtheroids, contaminants
   Cerebritis, brain abscess
   Confusion, altered LOC, seizure, movement
   Mortality 22% in older patients with CNS dz
   20% of all cases of bacterial meningitis in patients
    over age 60
   Brain abscess: 10% CNS infections
      Usually due to bacteremia
      Concomitant meningitis in 25-40% (rare with other
       causes of brain abscess)
         Listeria… Big Points


   NOT uncommon in elderly
   Meningitis, encephalitis, focal brain abscess
   Add Ampicillin
   Diphtheroids in CSF: listeria unless proven otherwise
               TB Meningitis
       Tuberculous meningitis (most common)
       Intracranial tuberculomas
       Spinal tuberculous arachnoiditis

   Meningitis: inflammation from rupture of
    subependymal tubercle into subarachnoid space
   Basilar meningitis, CN palsies, hydrocephalus
   Subacute or chronic
   Initial neutrophilic pattern on CSF
   Very high CSF protein may be seen
   AFB smears often neg; need HIGH volume sent to lab
              Viral Meningitis

   Aseptic meningitis
   May be difficult to initially separate from partially
    treated bacterial meningitis (obligates empiric
    treatment for bacterial)
   Differentiate from true aseptic (drug related such as
    NSAIDs, paraneoplastic)
              Viral Meningitis


   Finland study: etiology found in 66% patients with
    aseptic meningitis
   Viral encephalitis: etiology only found in 36% cases
   Viral prodrome, sore throat, myalgias, ill contacts, GI
    complaints; summer/fall season
   Most common= enteroviruses (25%)
      Echoviruses
      Coxsackievirus
            Viral Meningitis


   Less common causes
      Adenoviruses: URI sxs, year round
      CMV, EBV, HIV, influenzae
      Measles, mumps, rabies, rubella, varicella
      ?future avian flu (usually not CNS sxs, more
       URI/pneumonia/ARDS and DIC)
Encephalitis: Specific Causes
    Encephalitis Lethargica…

   The Awakenings…
   1916: von Economo described CNS disorder with
    lethargy and Parkinsonian features following viral
    syndrome with pharyngitis
   1916-1927 epidemic; now sporadic cases
   1918: influenza pandemic, ?connection (?immune
    mediated process)
                  Encephalitis

   More likely to be viral
   Etiology only found in 35% cases
      HSV-1: 10% cases (but accounts for over 50%
       cases in patients over 50)
      HSV-2
      VZV (?up to 10% in some series)

       Tick or insect borne diseases: 10%
                  Encephalitis
   Acute Viral Encephalitis
      Direct viral infection of neuronal cells
      Perivascular inflammation
      Destruction of gray matter


   Post-Infectious Encephalomyelitis
      Follows viral or bacterial infection
      Demyelination of white matter
      ?autoimmune component triggered by infectious
       agent
           HSV Encephalitis

   2-4 cases/million people/year
   Acute infection or more commonly reactivation of
    latent infection (trigeminal nerve ganglion)
   Characteristic site of damage: temporal lobe
      MRI findings of necrosis in temporal lobe
      Necrosis = RBC s on CSF!
            HSV Encephalitis

   Dysphasia, bizarre behavior, seizures
   Abnormal EEG
   High mortality: 30% with treatment
   Survivors: 10% long term disability
   Fever +/-
   Treatment: Acyclovir (60-75% mortality without
    treatment)
    HSV Encephalitis: Big Points


   Odd behavior, think encephalitis
   If thinking encephalitis, add acyclovir
   RBCs on CSF (with xanthochromia or lack of clearing
    between tube 1 and 4), think HSV
   Temporal symptoms
   Temporal necrosis or abnormalities on MRI
    Arboviruses and Encephalitis


   Arbovirus: Arthropod Borne Virus
   RNA viruses transmitted by mosquitoes or ticks
   10 % cases of sporadic encephalitis (?higher in
    elderly, up to 50% cases during epidemics)
    Arboviruses and Encephalitis


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


   Flavivirus family:
      St Louis Encephalitis **
      Japanese Encephalitis
      California Encephalitis
      West Nile Virus **
   West Nile Virus and
Encephalitis in the Elderly
              West Nile Virus

   1937: West Nile district Uganda (mild cases)
   Middle east/ Israel (14% fatality)
   1996: outbreak in Romania (4% fatality)
   1999: NY outbreak (11% fatality)
   Subsequent west spread to most states
   2002: 4156 reported cases in US, 284 deaths
   2003: 9858 cases, 262 deaths
              West Nile Virus


   Season: summer
   Mosquito transmission (currently infects 43/ 174
    different types of North American mosquitoes)
   Other routes
      Placenta
      Lactation
      Transfusion
      Organ transplant
             West Nile Virus


   Disease of the elderly
   Higher mortality in elderly
   Other risk factors not clear (?maybe HTN and DM
    leading to better virus entry)
               WNV: Predictors
   Admission diagnoses:
      30%: aseptic meningitis
      15%: fever
      18%: viral infection
      14%: UTI
      10% pneumonia
      7% : encephalitis
      5%: probable WNV (year 2001)


   Mortality rates highest with:
   Initial diagnosis of encephalitis (35% of those who died),
   No headache (50% had HA, 7% those that died had HA),
    and
   Initial mental status changes
                        WNV
   Presenting symptoms
      HA, fever, mental status changes
      CN findings, optic neuritis
      Myoclonus


   Flaccid Paralysis
      With or without encephalitis
      Asymmetric weakness/paralysis, no sensory loss
      Anterior horn cells (polio like)
      Absent DTRs
                     WNV
   Movement Disorders
     Parkinsonian
     Tremors
     Bradykinesia
     Cogwheel rigidity
     Postural instability
     Masked facies
     80-100% will have rest or intention tremor
     30% will have myoclonus
            WNV: Diagnosis


   High index of suspicion
   CSF: usually 200 TNC; 5-10% can have over 500 TNC,
    5% with < 5 TNC
   CSF with 50% neutrophils
   Elevated CSF protein
   CSF for ab studies: anti WNV ab, and negative SLE
    IgM (up to 40% cross reactivity in earlier studies)
              WNV: Treatment

   ?nucleoside analogues (ribavirin – no benefit in Israel)
   Human Immunoglobulin : protective antibodies
    (patients from Israel with high titers of anti-WNV ab);
    if effective, only in early disease
   ?vaccine development (effective in horses in 2001)
   ?inactivated JEV vaccine?
Meningitis and Encephalitis:
           Others
     Tick-Borne Diseases
 RMSF **
 Lyme Disease **
 Ehrlichiosis **
 STARI **
 Tularemia
 Babesiosis
 Colorado Tick Fever
Rocky Mountain Spotted Fever
   Rickettsia rickettsii
      Gm negative intracellular bacteria
      Endothelial cells: small vessel vasculitis


   Southeast, summer
   Dog Tick, Wood Tick
   2nd most common tick-borne illness

       Fever/headache/nausea/rash 80%
       Rash: blanching maculopapular, palms/soles,
        spreads centrally, later petechial and purpuric
       Hyponatremia, thrombocytopenia, inc ALT
       CSF: inc TNC, inc protein; neg gram stain
            RMSF: Diagnosis


   Clinical suspicion
   Low threshold to empirically treat
   Rash may be absent in 20%
   RMSF serologies: initial may be negative; need
    convalescent titers several weeks later
           RMSF: Treatment

   Doxycycline 100 BID
   Do not delay
   ?newer quinolones: probably, but no studies and no
    recommendations
   No indication for prophylactic treatment after
    uncomplicated tick bite
   Prevention: frequent inspection
            RMSF: Big Points

   Empiric Treatment if even suspected
   In North Carolina, any fever, HA, neuro syndrome will
    need treatment
   First serology titers NOT reliable
   Hyponatremia, low platelets, elevated LFTs, think
    RMSF…
   Do not wait for the rash…
               Lyme Disease
   Borrelia burgdorferi
   Deer Tick (smaller)
   NE/Great Lakes, but reported in almost all

   Stages
      1: erythema migrans rash, viral-like syndrome
      2. early disseminated phase, secondary cutaneous
      3. late/chronic: arthritis, cns involvement (CN
       palsies), myocardial damage
                        STARI

   Southern Tick Associated Rash Illness
   Lyme-like infection in North Carolina with negative
    Lyme serologies
   Lone Star Tick
   Borrelia lonestari
                    Ehrlichia
   “Rashless” RMSF
      Fever, headache
      CSF: pleocytosis, neg gm stain, inc protein
   Hyponatremia, thrombocytopenia, elevated LFTs
   Lone Star tick, Dog Tick
   Same treatment as RMSF
   Serologies and convalescent titers
Overall Picture: Diagnosis
   Difficult to initially separate meningitis from
    encephalitis in elderly; both present with mental
    status changes; elderly with meningitis less likely to
    have fever
   Other infections cause delirium in elderly
   Red flags
      Any CNS focality
      Behavioral changes/personality changes
      Seizures
      Lack of other source of infection
      Headache, ? nuchal rigidity, ill contacts
      Season, outdoor activity
      Low threshold to do LP
              Overall Picture
   Main Players
     Strep pneumoniae
     Listeria
     Viral agents such as enteroviruses
     HSV
     Arboviruses (including WNV now)
     Tick-borne bacteria (RMSF, ehrilchia, STARI)
    If things are not adding up…
   Less common causes
      VZV
      Rabies virus
      Post-measles, mumps, cmv, ebv
      Adenoviruses
      TB
      Protozoa
      Cryptococcus
      Gm negatives: klebsiella, e coli
                     Diagnosis

   CSF
       Elevated protein least specific
       Acute bacterial meningitis usually has high TNC,
        low glu, unless partially treated or listeria
       More than 2-3 TNC is not normal
       Gram stain, culture, PCR for HSV, viral studies for
        enteroviruses, serologies for arboviruses
       Latex agglutination studies: NOT helpful
       Serum for RMSF/ehrlichiosis titers: initial and
        convalescent titers
                   Treatment


   Initial empiric treatment
   OK to shotgun pending culture and test results the
    first 24 - 48 hours!
   Risk of s. pneumoniae resistance and high mortality of
    untreated disease – vancomycin initially
Treatment: Dexamethasone

   Acute bacterial meningitis
   Decreased mortality/morbidity (20 min prior to abx)
   Recommended: proven S. pneumoniae, high
    opening pressure, pos gm stain
   Not clear with other causes, subgroups like elderly
   Probably not bad effects with viral causes
   Dose: .4 mg/kg Q 6 hrs for 2-4 days
   ?decrease vancomycin crossing blood-brain barrier
        Treatment Summary

   Vancomycin
   Ceftriaxone/cefotaxime
   Ampicillin
   Acyclovir
   Doxycycline
   ?dexamethasone
   OK to cover for all for first 24-48 hours, then narrow
    based upon CSF results and serologies
                        CASES

   1. Active 78-y/o man with prior hx of aortic valve
    replacement years ago, presents with fever, slight
    confusion, dehydration.
   Initial concern for SBE, but CSF :TNC of 20.
   His serum Na 128. All cultures negative.
   What would the DDX include?
                       CASES


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

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


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