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

What are normal CSF findings? Protein 0.45 gm/L Elevated with Diabetes Elevated with neuropathies of any cause Elevated with increasing age Elevated by bleeding into the CSF (SAH or traumatic) 0.01 gm/L for every 1000 RBC’s

What are normal CSF findings? Glucose 60 % of blood glucose In persons with hyperglycemia it takes several hours for CFS and blood glucose to equilibrate Low CSF glucose Bacterial infection Tuberculosis, cryptococcosis, carcinomatous SAH Sarcoidosis Occasional viral

What are normal CSF findings? Cell count <5 WBC (all mononuclear) and < 5 RBC considered “normal” Traumatic tap WBC/RBC ratio = 1:1000 Pressure <20 In patients with bacterial meningitis wide range 40% >30, 10% < 14

Look at the whole pattern! Can the CSF reliably distinguish between a bacterial and non-bacterial cause of meningitis? Usually Look at the whole pattern!

Can the CSF reliably distinguish between a bacterial and non-bacterial cause of meningitis? Glucose <2.5 suggests bacterial < 0.5 highly suggests bacterial Protein > 2.5 suggests bacterial Cell count >500 suggests bacterial >1000 highly suggests bacterial % polys >50 suggests bacterial

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 TB can have predominance of polys

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 typical clinical presentation of bacterial meningitis? History Headache: 75-90% Photophobia: uncommon Examination Fever: 95% Stiff Neck: 85% Altered mental status: 80% All three: 40% Any one of the three: 100%

How “good” are Kernig and Brudzinski signs? Originally related to severe, advanced TB meningitis (not bacterial) Not studied in a prospective study until 2002 (N=297)* Sensitivity 5% Specificity 95% *Thomas KE et al. Clin Infect Dis. 2002;35:46-52

What are the common causes of bacterial meningitis? It depends upon age and risk factors Age Neonates: listeria, group B streptococci, E. coli Children: H. influenza 10 to 21: meningococcal 21 onward: pneumococcal >meningococcal Elderly: pneumococcal>listeria Risk factors Decreased CMI: listeria S/P neurosurgery or opened head trauma: Staphylococcus, Gram Negative Rods Fracture of the cribiform plate: pneumococcal

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

What is the proper empirical antibiotic regimen for presumed bacterial meningitis? Neonates 3rd generation cephalosporin and ampicillin Children 3rd generation cephalosporin Normal adult 3rd generation cephalosporin and vancomycin (if resistant pneumococci) Problems with cell mediated immunity (AIDS, steroids, elderly) Add coverage for listeria with ampicillin or co-trimoxazole S/P CNS trauma or neurosurgery Coverage for staphylococcus and gram negative rods with antipseudomonal beta-lactam and vancomycin

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? (today)

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

Do you need to do a CT scan before an LP? Usually not A CT scan should never delay therapy (obtain blood cultures)

Do you need to do a CT scan before an LP? Prospective studies* N = 412 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 Papilledema *Gopal et al. Arch Intern Med. 1999;159:2681-5 Hasbun and Abrahams. N Engl J Med 2001:345:1727-33

How contagious is meningitis? Are we at risk when we care for a patient? Not really The only bacterial meningitis that is spread from person to person is meningococcal The risk is very low Household contacts have about a 1% risk Health care workers have not been shown to have a risk After 24 hours of treatment this is no risk

What is “Aseptic” meningitis? It is a term used to mean non-pyogenic bacterial meningitis It describes a spinal fluid formula that typically has: A low number of WBC A minimally elevated protein A normal glucose It has a much bigger differential diagnosis than viral meningitis.

What are the treatable causes of aseptic meningitis/encephalitis syndrome? Infectious HSV 1 and 2 Syphilis Listeria (occasionally) Tuberculosis Cryptococcus Leptospirosis Cerebral malaria African tick typhus Lyme disease Non-Infectious Carcinomatous Sarcoidosis Vasculitis Dural venous sinus thrombosis Migraine Drug Co-trimoxazole IVIG NSAIDS

Generally advanced with CD4 < 100 Sub-acute onset: fever, headache What are the important things to know about AIDS- associated cryptococcal meningitis? Generally advanced with CD4 < 100 Sub-acute onset: fever, headache Stiff neck is rare Mortality with treatment is about 15%! Predictors of death Altered Mental status, low CSF WBC count, high CSF cryptococcal antigen titer

What are the important things to know about AIDS- associated cryptococcal meningitis? CSF findings Elevated pressure is the usual (>70%) Rest of CSF findings are often unimpressive WBC <50 Glucose: normal or slightly low Protein: normal or slightly elevated 25% have normal WBC, glucose and protein CSF cryptococcal antigen: 95-100% sensitive

What are the important things to know about AIDS- associated cryptococcal meningitis? Treatment Medical Induction: amphotericin B 0.7mg/kg x 2/52 (flucytosine) Consolidation: fluconazole 400 mg x 8/52 Maintenance: fluconazole 200 mg Pressure Daily LP’s to keep opening pressure <20 If LP’s are still needed after 1 month shunt

Questions from the Audience?

Meningitis – Who was awake? Which of the following are true statements? Early viral meningitis can have a predominance of polys Some viral meningitis can have low CSF glucose Listeria meningitis can have predominance of mononuclear cells rather than polys All of the above

Meningitis – Who was awake? Which of the following are true statements? Early viral meningitis can have a predominance of polys Some viral meningitis can have low CSF glucose Listeria meningitis can have predominance of mononuclear cells rather than polys All of the above

Meningitis – Who was awake? To correct CSF protein concentrations for blood in the CSF the proper ratio is approximately 0.01 gm/L of protein for every 100 RBC’s True False

Meningitis – Who was awake? To correct CSF protein concentrations for blood in the CSF the proper ratio is approximately 0.01 gm/L of protein for every 100 RBC’s True False

Meningitis – Who was awake? Which of the following are true about cryptococcal meningitis? a. A normal CSF effectively rules out cryptococcal meningitis b. If the CSF pressure is elevated one should not remove more than 10 ml at a time c. Everyone with HIV infection is at increased risk for cryptococcal meningitis.

Meningitis – Who was awake? Which of the following are true about cryptococcal meningitis? a. A normal CSF effectively rules out cryptococcal meningitis b. If the CSF pressure is elevated one should not remove more than 10 ml at a time c. Everyone with HIV infection is at increased risk for cryptococcal meningitis. None

Meningitis: References 1. Gopal AK, Whitehouse JD, Simel DL, Corey GR. Cranial computed tomography before lumbar puncture. A prospective clinical evaluation. Arch Intern Med. 1999;159:2681-5 2. Hasbun R, Abrahams J, Jekel J, Quagliarello VJ. Computed tomography of the head before lumbar puncture in adults with suspected meningitis. N Engl J Med 2001:345:1727-33 3. Blazer S, Berant M. Bacterial meningitis: Effect of antibiotic treatment on spinal fluid. Am J Clin Pathol. 1983;80:386 4. de Gans J, van de Beek D. N Eng J Med. 2002;347:1549-56 5. Hussein AS, Shafran SD. Acute bacterial meningitis in adults. Medicine 2000;79:360-68 6. Aronin S, Peduzzi P, Quagliarello VJ. Community acquired bacterial meningitis: Risk stratification for adverse clinical outcome and effect of antibiotic timing. Ann Intern Med 1998;129:862