Meningitis Matthew Grant MD
Objectives Understand the diagnostic accuracy of clinical findings Appreciate the differential diagnosis of aseptic meningitis syndrome, and indications for hospitalization Understand the initial antibiotic Rx for presumptive bacterial meningitis, and secondary prevention strategies
Meningitis - clinical presentation Classic triad <50% Fever alone VERY sensitive Stiff neck Altered cognition Headache 90% have 2 of 4 symptoms Thought of as acute illness but common for fever > 1 week Van de Beek et al. Clinical features and prognostic factors in adults with bacterial meningitis. NEJM 2004. 351(18):1849.
Kernig/Brudzinski signs Both suffer from very low sensitivity ~ 5% Thomas et al. Diagnostic accuracy of Kernig s sign, Brudzinski s sign and nuchal rigidity in adults with suspected meningitis. CID 2002. 35(1): 46.
More sensitive signs Nuchal rigidity passive/active inability to touch chin to chest 30% sensitivity Jolt accentuation of headache Pt rotates head horizontally 2x/second + if HA worsens 97% sens / 60% specific Uchihara and Tsukagoshi. Jolt accentuation of headache: the most sensitive sign of CSF pleocytosis. Headache. 1991. 31(3): 167.
Aseptic meningitis syndrome Meningitis with negative bacterial cultures Generally self limited illness with high proportion of etiologies remaining elusive despite testing Is there a test that safely allows ER discharge after LP results available?
Differential diagnosis of aseptic meningitis Infectious Viral Entero/echoviruses Acute HIV HSV2 > VZV, HSV1, CMV Mumps LCMV Bacterial Lyme > RMSF, ehrlichia Syphilis TB Fungal Coccioides Cryptococcus (+/- HIV) Parasitic Noninfectious Drug induced NSAID Bactrim IVIG Inflammatory Sarcoid > lupus Leptomeningeal carcinomatosis Craniopharyngioma
Lumbar puncture To CT first? Proceed if low concern for space occupying lesion w/ mass effect Under 60 Immune competent No h/o seizure/cns disease Normal neurologic exam 97% NPV for normal CT Hasbun et al. CT of Head before LP in adults with suspected meningitis. NEJM 2001; 345(24): 1727.
Classic CSF profiles Normal Aseptic meningitis Bacterial meningitis WBC <5 No polys Elevated, generally < 1000 Lymphocytic >1000 Neutrophilic Protein < 50 mg/dl 50-250 > 250 Glucose > 2/3 serum > 2/3 serum <45 Caveats 1. Early LP in an aseptic process can reveal neutrophilic pleiocytosis 2. Drug induced meningitis also is generally neutrophilic 3. TB/sarcoid/fungi/carcinoma (> LCMV/mumps) can cause low glucose
52 yr old male with RA on MTX presents in August with 1 day of HA and fever after recently trialing piroxicam for low back strain. He undergoes LP WBC 80 (60% polys), glucose 55, protein 105. Gram stain is negative for bacterial organisms. What do you do?
? A) Stop NSAID, discharge with reassurance and arrange office follow up the next day B) Send CSF for Lyme Ab, VDRL, HIV viral load, enterovirus and HSV PCR and empirically start IV acyclovir while awaiting test results C) Start dexamethasone/ceftriaxone/ vancomycin/ampicillin while awaiting gram stain/culture
Differentiating aseptic vs bacterial No pleiocytosis = not meningitis (exception is cryptococcal meningitis in AIDS) Sadly no single test excludes bacterial infxn in setting of pleiocytosis (most admit & give empiric abx if found) High specificity LP findings for bacterial infxn Glucose < 34 Protein > 220 WBC > 2000, polys > 1180 dx of acute meningitis. JAMA 1989. 262(19):2700. Spanos, Harrell and Durack. Differential
Microbiology of bacterial meningitis Adults Pneumococcus Meningococcus Listeria Group B strep GNR in elderly Brouwer, Tunkel and van de Beek. Epidemiology, Diagnosis and Antimicrobial Treatment of Acute Bacterial Meningitis. Clin Micro Rev 2010. 23(3):467.
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Need a clue?
Empiric treatment strategies Ceftriaxone Covers pneumococcus/mening/strep/gnr Dose first! + vancomycin To cover penicillin resistant pneumococcus + ampicillin if : <1 month, > 50 yrs, immunocompromised Cephalos inherently R to L. monocytogenes
If given, need to start before abx given and stop if etiology not pneumococcal Dexamethasone Dampens host WBC/cytokine response to bacteria RCT data shows Lowers mortality from pneumococcal meningitis from septic complications/sirs Improves hearing outcomes NOT change other neurologic outcomes
The beta lactam allergic patient Type 4 hypersensitivity reactions Ceftriaxone challenge Anaphylactic reactions Aztreonam Moxifloxacin
PREVENTION
For which traveler is vaccine prophylaxis of CNS infection NOT indicated? A) Married couple leaving for VFR trip to Pakistan B) 26 yr old biochem PhD student travelling to remote area of Amazon basin for 6 month work project C) Retiree planning a safari in Kruger NP, S. Africa D) 18 yr old backpacking through rural Thailand/Cambodia for 4 months E) 32 yr old Reuter s journalist travelling to Lagos, Nigeria for work over Xmas
Prevention of Meningitis Meningococcal vaccine Adults indications Terminal complement deficiency (also C3, properdin, factors D/H) Microbiologists Military recruits Travelers to high endemic zones Asplenic Consider MSM, esp HIV+ or contact with MSM from NYC given 12 outbreak
Meningococcal cont d Products Conjugate vaccines to capsular types A/C/Y/W135 recommended by ACIP Pro - better duration of seroprotection vs polysaccharide/ MPSV4 Vu et al. Ab persistence 3 yrs after immunization of adolescents with quadrivalent meningococcal conjugate vaccine. JID 2006. 193(6) 821. Con more local reactions Serotype B vaccine approved in Europe 13. Challenge to develop -- molecular similarity to human ICAM. Only serologic data available at this time Schedule q 5 yrs while at risk
Other vaccines Bacterial Pneumococcal No data to suggest either PPSV or PCV H flu type B Viral Polio Japanese encephalitis
Case 31 yr old woman with a history of 3 distinct episodes of aseptic meningitis, all self limited without rx. During most recent admit, PCR + for HSV2. She asks you about prophylactic antiviral treatment to stop these attacks. What do you tell her?
Mollaret s disease -- Benign recurrent lymphocytic meningitis: To prophylax or not? Aurelius et al. Long term valacyclovir suppressive treatment after HSV2 meningitis: a double blind RCT. CID 2012. 54(9): 1304. HSV 2 aseptic meningitis tends to recur RCT: 101 pts with HSV2 meningitis given either placebo or valacyclovir 500 bid x 1 yr and followed x 2 yrs Results: Statistically higher hazard of meningitis higher in the valacyclovir group during year 2 (no difference during year 1)