Meningitis, Encephalitis &
Rabies
Overview
• Meningitis
– The most board relevant topic
• Encephalitis
• A few brief words about Rabies
Definitions
• Meningitis is an
inflammation of the
membranes that
cover the brain and
spinal cord.
• Encephalitis is an
inflammation of the
brain
Meningitis
• Typical pathogens depend on the age of the
host and the presence of comorbidities
• Impaired cellular immunity (HIV, steroid use,
transplant, cytotoxic chemotherapy) increases
risk of Listeria monocytogenes
• Impaired humoral immunity (splenectomy,
hypogammaglobulinemia, multiple myeloma)
increase risk of S. pneumoniae
• Differential diagnosis of acute meningitis
includes infectious and noninfectious causes
Differential Diagnosis of Infectious Causes of Acute Meningitis
Viruses
Nonpolio enteroviruses
Arboviruses
Herpesviruses (HSV, VZV, CMV,
EBV and HHV-6)
Lymphocytic choriomeningitis virus
HIV
Adenovirus
Parainfluenza virus type 3
Influenza virus
Measles virus
Rickettsiae
Rickettsia rickettsii
Rickettsia conorii
Rickettsia prowazekii
Rickettsia typhi
Orientia tsutsugamushi
Ehrlichia and Anaplasma spp.
Bacteria
Haemophilus influenzae
Neisseria meningitidis
Streptococcus pneumoniae
Listeria monocytogenes
Escherichia coli
Streptococcus agalactiae
Propionibacterium acnes
Staphylococcus aureus
Staphylococcus epidermidis
Bacteria continued
Coxiella burnetii
Mycoplasma pneumoniae
Enterococcus spp.
Klebsiella pneumoniae
Pseudomonas aeruginosa
Salmonella
Acinetobacter
Viridans streptococci
Fusobacterium necrophorum
Stenotrophomonas maltophilia
Streptococcus pyogenes
Pasteurella multocida
Bacillus anthracis
Capnocytophaga canimorsus
Nocardia spp.
Mycobacterium tuberculosis
Spirochetes
Treponema pallidum
Borrelia burgdorferi
Leptospira
Protozoa and helminths
Naegleria fowleri
Angiostrongylus cantonensis
Baylisascaris procynonis
Strongyloides stercoralis
Expanded from PPID 7th ed.
Noninfectious Etiologies of Acute Meningitis
Other infectious syndromes
Parameningeal foci of infection
Infective endocarditis
Viral postinfectious syndromes
Postvaccination (mumps, measles, polio, pertussis,
rabies, vaccinia)
Noninfectious etiologies and diseases of unknown etiology
Intracranial tumors and cysts
Craniopharyngioma
Dermoid/epidermoid cyst
Teratoma
Systemic illness
Systemic lupus erythematosus
Vogt-Koyanagi-Harada syndrome
Medications
Antimicrobials
Trimethoprim
Sulfamethoxazole
Ciprofloxacin
Penicillin
Isoniazid
Metronidazole
Cephalosporins
Pyrazinamide
NSAIDs
Muromonab-CD3 (OKT3)
Azathioprine
Cytosine arabinoside (high dose)
Carbamazepine
Immune globulin
Ranitidine
Phenazopyridine
Miscellaneous
Procedure-related
Postneurosurgery
Spinal anesthesia
Intrathecal injections
Chymopapain injection
Seizures
Migraine or migraine-like syndromes
Mollaret’s meningitis
PPID 7th ed
Acute Bacterial Meningitis
PPID 7th edition
Clinical Presentation
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Headache (>90%)
ABM can be excluded in a
patient with none of these
Fever (>90%)
symptoms
Meningismus (>85%)
Altered sensorium (>80%)
Vomiting (35%)
Seizures (30%)
Focal neurologic findings (10-20%)
Papilledema (<5%)
JAMA 282 (2): 175-181, 1999
PPID 7th ed Chapter 84
Clinical Presentation
• Kernig’s sign and
Brudzinski’s sign both
classically described
but poor diagnostic
sensitivity
JAMA 282 (2): 175-181, 1999
Pop Quiz
• Which physical exam maneuver has the
highest sensitivity for meningitis?
Jolt Accentuation of Headache
• Asking the patient to move their head side
to side at a rate of 2-3x/min
• Sensitivity of 97% and Specificity of 60%
• Very High negative predictive value
Uchihara, T. Headache. 1991
Clinical Presentation
• N. meningitidis is present
in 73% of patients with
ABM who have a rash
(petechial)
• Differential diagnosis
includes RMSF,
echovirus type 9, S.
pneumoniae, H.
influenzae, Acinetobacter
and Staphylococcus
aureus meningitis with
sepsis
Diagnosis & Treatment
Who needs a head CT prior to lumbar puncture?
Characteristics of Cerebrospinal Fluid Analysis in Meningitis
Normal CSF
Opening pressure (cm H2O)
5-20
Bloody Tap
Normal
WBC count (cells/mm3)
<10 monocytes
< 1 PMN
WBC:RBC 1:700
RBC count (cells/mm3)
<2
WBC:RBC 1:700
Protein (mg/dl)
<45
Glucose (mg/dl)
>50% serum levels
Viral Meningitis
Bacterial meningitis
Normal to mildly elevated
10-1000 lymphocyte
predominance
>18
1000-5000 PMN
predominance
Normal
Normal
15-45
Normal
100-500
Normal
Normal
<40
10% of ABM presents with lymphocyte predominance
Up to 50% of West Nile virus patients have neutrophil predominance
Modified from Bartlett JG, Pocket book of infectious disease therapy, 10th ed, Baltimore, 1999
CSF Gram staining
• Sensitivity correlates with bacterial load
– 25% of pts with < 103 CFUs/ml have + gs
– 97% of pts with > 105 CFUs/ml have + gs
• Sensitivity also correlates with pathogen
– S. pneumoniae
– H. flu
– N. meningitidis
– GNR
– Listeria
90%
86%
75%
50%
30%
PPID 7th ed. Ch 84
Gram positive lancet-shaped diplococci of Streptococcus pneumoniae
Listeria monocytogenes Infections. Cerebrospinal fluid shows characteristic gram-positive rods
(Gram stain). Listeriosis is much more common among patients with human immunodeficiency
virus infection or acquired immunodeficiency syndrome compared with the general population.
Neisseria meningitidis: Gram negative diplococci on CSF Gram stain
CSF culture
• Positive in 70-85% of patients who have
not received prior antimicrobial therapy
• Cultures may take up to 48 hrs for
identification
Steroids in Adults with Bacterial
Meningitis
• Routine use of dexamethasone is warranted in
most adults with suspected pneumococcal
meningitis
• If the meningitis is found not to be caused by S.
pneumoniae, dexamethasone should be
discontinued
• Should be given before or with first dose of abx
• If the strain is highly resistant to PCN or
cephalosporins “careful observation and followup are critical”
MKSAP 14
Item 16
Gram Positive Diplococci
MKSAP 14
Item 14
Viral Meningitis/Encephalitis
Nonpolio enteroviruses
Echoviruses
Coxsackieviruses
Enterovirus-71
Herpesviruses
HSV, VZV, CMV,
EBV and HHV-6
Lymphocytic choriomeningitis virus
Mumps virus
HIV
Adenovirus
Parainfluenza virus type 3
Influenza virus
Measles virus
Arboviruses
Mosquito-borne
California
St. Louis
Eastern equine
Western equine
Venezuelan equine
West Nile virus
Tick-borne
Colorado tick fever
Powassan
Enteroviruses
• Leading recognizable cause of aseptic
meningitis
• 30,000 – 75,000 U.S. meningitis cases/yr
• Marked summer/fall seasonality in temperate
climates
• Periods of warm weather and wearing sparse
clothing facilitate fecal-oral spread
• PCR on CSF and supportive therapy
• Newly described Enterovirus-71 can cause
anterior myelitis
Arboviruses
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California (La Crosse)
St. Louis
Eastern Equine -- 50-70% mortality
Western Equine
Venezuelan Equine
West Nile
Colorado tick fever
West Nile Neuroinvasive Disease
• WNV is now the most common cause of
epidemic viral encephalitis in U.S.
• WNV infection
– Asymptomatic 80%
– West Nile Fever 20%
– Neuroinvasive disease <1%
• Meningitis 40%
• Encephalitis 60%
• Acute flaccid paralysis/poliomyelitis
– 5-10% of all patients with neuroinvasive disease
– 4 cases/100,000 population during a WNV epidemic
Ann Neurol 2006; 60:286-300
www.cdc.gov
www.cdc.gov
West Nile Virus Screening of Blood Donations and
Transfusion-Associated Transmission --- United
States, 2003
• In 2002, transfusion-associated transmission of
WNV recognized
• In June 2003, nucleic acid amplification tests
(NATs) for WNV applied to screen all blood
donations
• 6 million units screened
– 818 positive viremia
– 6 cases negative screen by NAT that transmitted
WNV
MMWR April 9, 2004 / 53(13);281-2
Distinguishing WNV, Enterovirus-71, Poliomyelitis and
Guillain-Barre Syndrome
Coastal marshes
June, July, August
Age <10, >55 yrs
Unique clinical features CSF WBC >1000
Mortality 50-70%
Sequelae 80% (esp children <10yrs)
West, midwest
Infants and adults >50 years old
5-15% mortality
Sequelae: moderate in infants and low in others
Mostly LaCrosse Virus
Woodlands; June-September
Children <20
Unique clinical feature: seizures
Mortality <1%
Sequelae rare <2%
US, Canada, Caribbean (urban and rural)
June, July, August
Unique clinical feature: dysuria
Mortality 2 – 20%
Sequelae 25%
HSV meningitis
• Can be complication of primary genital infection (more
common with HSV-2)
– 36% of women and 13% of women with primary genital HSV-2
infection had stiff neck, headache and photophobia
– Hospitalization was required in 6.4% of women and 1.6% of men
for aseptic meningitis in association with primary HSV-2
infections
• Meningeal symptoms start 3-12 days after onset of
genital lesions
• Use of antiviral therapy early for genital lesions
decreases subsequent development of aseptic
meningitis
• Association with recurrent aseptic meningitis
HSV Encephalitis
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Biphasic age distribution
Temporal lobe disease
Focal neurologic findings
Diagnosis CSF PCR (culture) and MRI
Therapy IV Acyclovir
Outcome
– Mortality 15%
– Morbidity 50%
MKSAP 14
Item 120
Diseases which mimic HSE
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St. Louis encephalitis
Western equine encephalitis
California encephalitis
Eastern equine encephalitis
EBV
CMV
West Nile Encephalitis does not appear
Echovirus
to mimic Herpes Simplex Encephalitis
PML
SSPE
HHV-6
• Infects nearly all humans by age 2 years
• Exanthem subitum (roseola, Sixth dz)
• Immunocompromised hosts
– Reactivation in 1/3 of solid organ transplant pts and 1/2
of BMT pts by 4 weeks posttransplant
– GVHD, delayed bone marrow engraftment, encephalitis,
hepatitis, interstitial pneumonitis
– Epiphenomen of immunocompromise?
– Promotes CMV or other pathogens?
– Quantitative PCR needed on CSF to invoke as etiologic
agent of meningitis/encephalitis
Eosinophilic Meningitis
Nematodes
• Angiostrongylus
cantonensis
• Gnathostoma
spinigerum
• Baylisascaris
procyonis
• Toxocara canis
Cestodes
• Taenia solium
Trematodes
• Paragonimus
westermani
• Schistosomiasis
• Fascioliasis
Eosinophilic Meningitis
Nonparasitic
• Coccidiomycosis
• Cryptococcosis
• Myiasis
Noninfectious
• Idiopathic
hypereosinophilic
syndrome
• Leukemia/lymphoma
• Cipro/Bactrim
• Intraventricular
gentamicin/vanc
• NSAIDS
• Myelography contrast
Angiostrongylus cantonensis
• Adults reside in
pulmonary arteries of
rats
• Eggs hatch in the
lungs, the larvae are
swallowed, expelled in
feces and seek an
appropriate molluscan
intermediate host
• Develops into infective
larvae in:
– Slugs, land snails
– Freshwater prawns,
land and coconut
crabs, frogs
Angiostrongylus cantonensis
• Epidemics and sporadic infections reported in
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South Pacific
Southeast Asia
Tawain
Jamaica, Cuba, Egypt
• Recognized sources of human infection
– Raw or undercooked snails, prawns, crabs
– Contamination of leafy vegetables by larvae
deposited by slugs or snails
– Caesar salad recognized in one epidemic
Angiostrongylus infection
• Disease self-limited
• Rare fatal cases (massive inoculum)
• Incubation period 1-6 days after ingestion
of infected snails
• HA, stiff neck, fever, rash, pruritus,
abdominal pain, nausea, vomiting
• Paresthesias – chest wall, face, limbs
• Cranial nerve palsies (fourth and sixth
most common)
Angiostrongylus treatment
• Supportive care
• Killing larvae in and around the brain may
be detrimental
• Repeated lumbar punctures helpful in
treating headaches
• Recovery usually complete by 2 months
• Corticosteroids decrease duration of
headaches
CID 2000; 31: 660-2
Baylisascaris procyonis
• Ascarid of raccoons
• Visceral larval migrans in humans
• Severe and commonly fatal eosinophilic
meningoencephalitis occurs in more than half
the cases
• Eye involvement is common
• Diagnosed by detecting larvae in tissue
• Experimental serology
• Albendazole and steroids are commonly tried
Bayliscariasis
• Severity of disease
– Number of eggs ingested
– Extent/location of larval migration
– Severity of ensuing inflammation and necrosis
Treatment
• Laser photocoagulation in ocular dz
• No cure for clinical disease
• Albendazole and dexamethasone used with
good CNS and ocular penetration
• Prophylaxis with albendazole on days 1-10 or
days 3-10 after exposure offers 95-100%
protection
• No children receiving albendazole after eating
raccoon feces have developed baylisascariasis
CID 2004: 39 (15 November)
Rabies
• Highest case fatality rate of any infectious
disease
• Let me say it again…
• 2-3 cases annually in USA
• Recent death in a returned OEF soldier
• Transmitted most often by bite from rabid
animal
• Transmission from tissue donors has also
been described
Source: Centers for Disease Control and Prevention, November 2010
Rabies
• Virus amplifies at inoculation site and
reaches CNS via motor/sensory nerves
• Moves centrally at a rate of 5-10cm/day
• Clinical Latency period 3-6 mos (7d-1yr)
• Nonspecific prodrome
– “flu like symptoms”
– Paresthesia or pain at site
Rabies
• Encephalitic Rabies (80%)
– Hydrophobia, aerophobia, pharyngeal spasms
• Paralytic Rabies (20%)
• Clinically similar to Guillan-Barre Syndrome
• Coma, paralysis and cardio/pulmonary
collapse with 2 weeks
Diagnosis/Treatment
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Sample of saliva, skin for PCR
Antibody from serum or CSF
Treatment is RIG and Vaccine after exposure
1 patient has survived (17 yo F from Wisconsin)
The “Milwaukee Protocol”
– Ketamine, Ribavirin, Amantadine
• Has not been successful in subsequent patients
Pre/Post Exposure
• Prior to exposure in high risk individuals
Questions/Comments?