1. Meningitis Commonly Asked Questions Stephen J. Gluckman, M.D.

2. Meningitis How do you make the diagnosis? The diagnosis is ruled in or out by examination of the CSF

3. 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

4. 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

5. 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

6. What are normal CSF findings? Cell count –< 5 WBC (all mononuclear) and < 5 RBC considered “normal” –Traumatic tap WBC/RBC ratio = 1:1000

7. Interpreting a CSF Formula Likelihood ratios for bacterial meningitis* –WBC > 50015 < 5000.3 –CSF Glucose/Blood Glucose < 0.418 > 0.60.3 * Straus SE, et al JAMA 2006

8. Can the CSF reliably distinguish between a bacterial and non-bacterial cause of meningitis? Usually Always look at the entire pattern

9. 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

10. 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

11. What are the treatable causes of aseptic meningitis/encephalitis syndrome? Infectious –Lyme disease –Syphilis –Listeria (occasionally) –Tuberculosis –Cryptococcus –Leptospirosis –Cerebral malaria Non-Infectious –Carcinomatous –Sarcoidosis –Vasculitis –Dural venous sinus thrombosis –Migraine –Drug TxS IVIG NSAIDS

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

13. 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.

14. What is the proper empiric antibiotic regimen for presumed bacterial meningitis? It depends upon the clinical situation

15. 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

16. What is the proper empirical antibiotic regimen for presumed bacterial meningitis? Normal adult –3 rd 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

17. 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? CASE 1 a.Initiate antibiotics b.High dose corticosteroids c.Head CT scan d.Lumbar puncture

18. Do you need to do a CT scan before an LP? Usually not A CT scan should never delay therapy

19. 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

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

21. 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?

22. 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

23. Steroids or no Steroids? Steroids (maybe)

24. 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

25. 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

26. 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

27. CASE 2 A 36 year old woman sees you on August 17 th 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 14WBC 18 with 70% lymphocytes Protein 68RBC 1 Gram stain: negative What tests would you order as part of the initial evaluation?

28. a.RPR b.CSF PCR for enteroviruses c.CSF PCR for HSV 1 and 2 d.ANA e.Head CT f.HIV serology

29. 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

30. 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

31. 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!

32. Questions ?