1. CSF: How certain can we be? Meira Louis PGY1

2. Objectives Present a published case highlighting the difficulties in CSF diagnosis Understand the objective evidence for the tests ordered on CSF Understand where clinical judgement falls in the spectrum of certainty

3. Sheila 21yo female 1 day history: –non-specific lethargy –Fever and rigors –Generalized headache –Nausea, vomiting PMX: –Childhood asthma –Hyperthyroidism Meds: –None Huynh et al, 2007

4. On exam: –Vitals: 38°C –Alert, oriented –Normal neuro Bloodwork –WBC: 19.5 –CRP: 185 –Lytes, LFTs, glucose Imaging: –Chest X-ray –Urinalysis –CT head

5. CSF – for what? Cell count Gram’s Stain Turbidity Xanthochromia Glucose Protein India Ink Cryptococcal Antigen Lactic Acid Bacterial Antigen tests Acid Fast Stain

6. Sheila’s CSF Clear and colourless Protein: 0.38 mg/dL Glucose: 3.6 mmol/L 12x10 6 RBC 1x10 6 WBC (all mononuclear) Negative gram stain

7. What would you do? What’s your diagnosis? How confident are you? How confident should you be?

8. Cell Count and Differential How many leuks are too many leuks? Does it matter what kind? –Monomorphic vs polymorphic –lymphocytosis Does prior abx change your cell count? Thomson et al, 2001.; Van de Beek, 2004.

9. What happens with a traumatic tap? Predicted WBC = CSF RBC x serum WBC serum RBC If WBC was more than 10x normal was 48% predictive of bacterial meningitis If less than 10x was 99% predictive of it NOT being meningitis Mayefsky et al. 1987

10. Glucose Hypoglycorrhachia If normal serum glucose: –Ratio of CSF:serum is 0.6:1 –Abnormal when less than 0.5 If elevated serum glucose: –Ratio of CSF:serum is 0.4:1 –Abnormal when less than 0.3

11. Protein Normal range in CSF: 15-45 mg/dL –Greater than 150 is probably bacterial –Greater than 1000 should suggest fungal Other causes? –Any meningitis –Subarachnoids –CNS vasculitis –Syphilis –Viral encephalitis –neoplasms

12. Gram Stain All common etiologies-no previous antibiotics75-90% All common etiologies-antimicrobial therapy prior to LP40-60% Streptococcus pneumoniae 90% Neisseria meningitidis 75% Haemophilus influenzae 86% Listeria monocytogenes <50% Gram-negative bacilli 50% What’s the sensitivity for bacteria? Gray et al, 1992

13. Other tests Lactic Acid Non-specific Elevations over 35 mg/dL may indicate bacterial meningitis Lactate may rise before glucose drops Serum Procalcitonin Very sensitive Not available for up to 24 hours

14. Back to the case… The following morning: –Diplopia, worsening headache –Temp increase to 40°C –GCS of 9 –No rash, no nuchal rigidity, no focal neuro Repeat CT scan with contrast IV ceftriaxone, gentamicin, and acyclovir were started Blood and CSF came back positive for N. meningitidis

15. On a reassuring note… SensitivitySpecificityAccuracy ER doc0.890.770.79 CSF leuk0.500.940.71 Glucose0.330.420.11 Protein0.630.940.75 CRP0.780.740.75 Procalcitonin0.871.000.99 Ray et al, 2006