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					       Meningitis
Commonly Asked Questions

 Stephen J. Gluckman, M.D.
           Meningitis
 How do you make the diagnosis?
• The diagnosis is ruled in or out by
  examination of the CSF
    How “good” are meningeal signs?
• Acute bacterial meningitis
    – Sensitivity *
       • Kernig’s: 5%
       • Brudzinski’s: 5%
       • Nuchal rigidity: 30%


*   Thomas KE, Hasbun R, Jekel J, et al. Clin Infect Dis
    2002;35:46-52
What are normal CSF findings?
• Protein
  – 23 to 38 mg/dL
  – Elevated with DM, neuropathies
  – Elevated with increasing age
  – Elevated by bleeding into the CSF (SAH or
    traumatic)
      • 1 mg/dL for every 1000 RBC’s
 What are normal CSF findings?
• Glucose
  – > 60% of blood glucose is normal, < 40% is abnormal
     • In persons with hyperglycemia it takes several hours
       for CFS and blood glucose to equilibrate
  – Low CSF glucose
     • Occasionally with viral meningitis
     • Bacterial infection
     • Tuberculosis, cryptococcosis, carcinomatous
     • SAH
     • Sarcoidosis
What are normal CSF findings?
• Cell count
  – < 5 WBC (all mononuclear) and < 5 RBC
    considered “normal”
  – Traumatic tap
     • WBC/RBC ratio = 1:1000
   Interpreting a CSF Formula
• Likelihood ratios for bacterial meningitis*
  – WBC
      • > 500               15
      • < 500               0.3
  – CSF Glucose/Blood Glucose
      • < 0.4               18
      • > 0.6               0.3
  *Straus SE, et al JAMA 2006
Can the CSF reliably distinguish between a
   bacterial and non-bacterial cause of
               meningitis?


                Usually

      Always look at the entire pattern
       Are there exceptions?
• Early viral can have a predominance of
  polys
• Some viral can have low CFS glucose
• Listeria can have predominance of
  mononuclear cells rather than polys

 If it looks like viral but you are not sure,
 observe and repeat the tap in 6-8 hours
  What is “Aseptic” Meningitis?
• IT SHOULD NOT BE LIMITED TO ONLY
  CONSIDERING VIRAL MENINGITIS
• “Aseptic” meningitis is shorthand for a certain
  spinal fluid formula
   – Lowish WBC count
   – Predominantly lymphocytes
   – Normal glucose
• Don’t use the term viral meningitis unless you
  prove it, think of it as “aseptic” meningitis
                  What are the
         treatable causes of aseptic
       meningitis/encephalitis syndrome?
• Infectious                    • Non-Infectious
  –   Lyme disease                – Carcinomatous
  –   Syphilis                    – Sarcoidosis
  –   Listeria (occasionally)     – Vasculitis
  –   Tuberculosis                – Dural venous sinus
  –   Cryptococcus                  thrombosis
  –   Leptospirosis               – Migraine
  –   Cerebral malaria            – Drug
                                      • TxS
                                      • IVIG
                                      • NSAIDS
How much does prior administration of
  antibiotics alter the CSF findings?




             Not Much
How much does prior administration of
  antibiotics alter the CSF findings?

• 48-72 hours of prior intravenous antibiotic
  treatment has little effect on glucose,
  protein and cell count
  – It will rarely change the CSF from a “bacterial”
    to an “aseptic” formula
• Prior antibiotic treatment will likely make
  the cultures negative.
What is the proper empiric antibiotic regimen
    for presumed bacterial meningitis?




   It depends upon the clinical situation
   What are the common causes of
    bacterial meningitis in adults?
• It depends upon age and risk factors
  – Age
     • 10 to 21: meningococcal
     • 21 onward: pneumococcal > meningococcal
     • Elderly: pneumococcal > listeria
  – Risk factors
     • Decreased CMI: ADD listeria to the list
     • S/P neurosurgery or opened head trauma:
       Staphylococcus, Gram Negative Rods
   What is the proper empirical antibiotic
regimen for presumed bacterial meningitis?

• Normal adult
  – 3rd generation cephalosporin and vancomycin
• Problems with cell mediated immunity
  (AIDS, steroids, elderly)
  – Add coverage for listeria with ampicillin or TxS
• S/P CNS trauma or neurosurgery
  – Coverage for staphylococcus and gram
    negative rods with anti-pseudomonal beta-
    lactam and vancomycin
                  CASE 1
A 21 year old previously healthy man is brought
to the emergency room with a one day history of
fever, mild photophobia and headache. On
examination he is awake and alert, there are no
focal neurological findings but his neck is
somewhat resistant to felxion. Blood cultures and
basic lab studies are obtained. The next step in
management should be?
 a. Initiate antibiotics
 b. High dose corticosteroids
 c. Head CT scan
 d. Lumbar puncture
Do you need to do a CT scan
       before an LP?




         Usually not

A CT scan should never delay therapy
     Do you need to do a CT scan
            before an LP?
• Prospective study*
   – N = 301
   – Predictors of CNS mass lesion
      • History
         – > 60 years old
         – Immunocompromised
         – Hx of prior CNS disease
         – Hx of seizure w/in 1 week prior to onset
      • Examination
         – Focal neurological findings
         – Altered mental status
*Hasbun and Abrahams 2001
How important is the speed of initiating
  antibiotics in bacterial meningitis?




                It is important
 But it is not the critical prognostic factor
How important is the speed of initiating
  antibiotics in bacterial meningitis?

• The clinical outcome is primarily
  influenced by the severity of the illness at
  the time antibiotics are initiated
  – Severity based on
     • Altered mental status
     • Hypotension
     • Seizures
How important is the speed of initiating
  antibiotics in bacterial meningitis?
• No factors
  – 9% with adverse outcome
• One factor
  – 33% with adverse outcome
• Two or three factors
  – 56% with adverse outcome


  Therefore, though treatment should be
  administered ASAP, the impact of antibiotic
  delay is a function of the severity of disease at
  the time that treatment is initiated
Steroids or no Steroids?




        Steroids
        (maybe)
      Steroids or no Steroids?
• Reduced morbidity and mortality
  – Only shown for pneumococcal meningitis in adults*
    and haemophilus meningitis in children
• Give before or at the same time as the first
  dose of antibiotics
• Dose studied
  – Dexamethasone 10 mg Q6H x 4 days

 * de Gans J. N Engl J Med 2002;347:1549-56
      Steroids or No Steroids
• However
  – Recent study from Malawi showed no benefit*
     • Did not show harm
     • Malawi (developing country) may not be
       generalizable
     • 90% were HIV (+)

    * Scarborough et al, N Engl J Med 2007;357:2441-50
        Steroids or No Steroids
• What to do today (my opinion)
  – I would use steroids
     • Makes pathophysiological sense
     • Proven benefit in animal model
     • Proven benefit for H. influenza in children
     • No evidence of harm
     • Good study in adults showing benefit
     • Malawi study may not apply to where I practice
  – But must use early
                         CASE 2
• A 36 year old woman sees you on August 17th for a 2
  day history of fever and progressive headache. She
  lives in an urban setting.
   – PMH: negative
   – Medications: none
   – Physical Examination: moderate nuchal rigidity, otherwise
     normal
   – A lumbar puncture reveals
      • OP 14                 WBC 18 with 70% lymphocytes
      • Protein 68            RBC 1
      • Gram stain: negative
• What tests would you order as part of the initial
  evaluation?
What tests would you order as part of the
initial evaluation?


a.   RPR
b.   CSF PCR for enteroviruses
c.   CSF PCR for HSV 1 and 2
d.   ANA
e.   Head CT
f.   HIV serology
   How can I narrow down the
possible causes of viral meningitis?

• Piece of cake!
• Consider the season
  – Summer/fall v. Winter/spring
• Consider the syndrome
  – Meningitis v. Encephalitis
   How can I narrow down the
possible causes of viral meningitis?
• Summer/Fall
  – Meningitis
    • Enteroviruses: polio, coxsackie, echo
  – Encephalitis
    • Arboviruses: West Nile, equine encephalitides
• Winter/Spring
  – Meningitis
    • Mumps
  – Encephalitis
    • Childhood: mumps, measles, varicella
   How can I narrow down the
possible causes of viral meningitis?
• Any time of year
  – Meningitis
     • HSV 2, HIV
  – Encephalitis
     • HSV 1, HIV
• That’s it!
Questions ?

				
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posted:7/25/2011
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