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 ?