Meningitis

Approach to the patient with suspected meningitis:

• Determine whether the suspected infection involves the subarachnoid space (meningitis) or whether there is evidence of either generalized or focal involvement of brain (cerebral hemispheres, cerebellum, or brainstem), which suggests encephalitis.  This is done mostly by history and PE.
• Encephalitis implies there has been direct injury to brain tissue is directly injured (usually by a viral infection)
• focal bacterial, fungal, or parasitic infections involving brain tissue are classified as cerebritis or abscess

 

History:

• Travel and exposure hx: ticks (lyme), rodents (LCMV)
• sexual activity, previous STIs (esp HSV)
• sick contacts (VZV exposure, TB, sick children)
• Medication use (NSAIDs, immunosuppresive medications)
• Classic triad of symptoms: Fever, Nuchal Rigidity, and Altered mental status - all 3 are rarely seen, but rare to have meningitis in the absence of at least one of those symptoms.
• Other symptoms include headache, photophobia, nausea/vomiting, neurological symptoms (seizures, focal deficits, hydrocephalus), and possibly petechial rash/purpura with meningococcal meningitis.

 

Physical exam:

• to differentiate meningitis from encephalitis or focal brain lesion, a complete neurologic exam is essential (including looking for papilledema)
• nuchal rigidity is the pathognomonic sign of meningeal irritation (neck resists passive flexion)
• Kernig's and Brudzinski's signs are also considered classic signs of meningeal irritation, but sensitivity is poor and specificity is uncertain.  Both can be absent/reduced in extremes of age, immunocompromised pts and pts with AMS  
• Kernig's sign: with the patient supine, the thigh is flexed on the abdomen, with the knee flexed; attempts to passively extend the knee elicit neck pain when meningeal irritation is present
• Brudzinski's sign: elicited when the patient is supine and is positive when passive flexion of the neck results in spontaneous flexion of the hips and knees
• On exam, remember that Brudzinski's sign and Kernig's sign are highly insensitive, but actually quite specific (~95%) - so arguably they are worth doing: if negative, not helpful, but if positive, be much more concerned! Nuchal rigidity is not particularly sensitive or specific.  Jolt accentuation test, whereby the patient horizontally moves head rapidly causing increased headache, is actually fairly sensitive > specific.

• Other PE clues: rash (maculopapular may suggest a viral exanthem; palms and soles can be affected in RMSF); parotiditis (suggests mumps, in an unvaccinated pt); vesicular genial lesions (HSV-2), thrush (HIV)

 

 

Microbiology of Bacterial Meningitis

Community-Acquired:

• Strep pneumo = most common
• Neisseria meningitides
• H.influenza
• Listeria.  Risk factors for Listeria = Age > 50, immunocompromised state, pregnancy, alcoholics

Healthcare-Associated: i.e. neurosurgery, VP shunts or EVDs, epidural procedures – worry about Staph (coag negative and S.aureus) and gram negatives including Pseudomonas

 

 

Lumbar puncture pearls:

• Lateral decubitus position, facilitates obtaining an opening pressure
• Try to obtain 4 tubes (5 mL each)
• Send the first and fourth tube for cell count and differential (as the RBCs may be high in the first tube if it was a traumatic tap)
• Peripheral blood in the CSF after a “traumatic tap” will result in an artificial increase in WBCs by one WBC for every 500 to 1,000 RBCs in the CSF
• Additional routine studies: protein, glucose, culture (bacterial, fungal, mycobacterial, viral), gram stain and AFB smear
• Others test to consider: specific antigen tests (ie. crypto), PCR for HSV, enteroviruses etc., antibody levels against microorganisms (ie. cocci), immunoelectrophoresis for -globulin level and oligoclonal bands, and cytology.
• 15 mL of CSF is sufficient to obtain all of the listed studies, but the the yield of fungal, mycobacterial cultures and cytology increases when larger volumes are sampled. In general 20–30 mL may be safely removed (in adults)

 

 

Indications for CT scan before LP – 2004 IDSA Guidelines

Main concern is unrecognized increased ICP, whereby LP leads to cerebral herniation and death.

1. Immunocompromised state – higher risk of mass lesions including abscesses and malignancy
2. Focal neurological deficits
3. History of CNS disease – mass lesion, major CVA
4. New onset Seizures within 1 week of presentation
5. Papilledema on exam
6. Abnormally decreased mental status – partially because you cannot do a neuro exam

Seriously consider memorizing these criteria, because it turns out most patients do NOT need a CT scan prior to LP, and this just leads to needless delay in diagnosis and treatment.

Note that our patient actually met 2 criteria for CT scan - her mental status and her focal neurological deficit (with her left facial droop).  Do not forget these indications for CT scan prior to LP otherwise you will look bad like the OSH doctors.

 

 

CSF findings in Meningitis:

CSF parameter	Bacterial	Viral	TB	Cryptococcal
OP (mmH20)	200-500	<250	180-300	>200
WBC	1000-5000	50-1000	50-300	20-500
Differential	Neutrophils	Lymphocytes	Lymphocytes	Lymphocytes
Glucose	<40	>45	<45	<40
Protein	100-500	<200	50-300	>45
Gram stain	+ 60-90%	Neg	Neg	Neg
AFB	Neg	Neg	+ <25%	Neg
India ink	Neg	Neg	Neg	+ >60%
Crpto Ag	Neg	Neg	Neg	+ >85%
Culture	+ 75-85%	Neg	+ 25-86%	+ >95%

 

 

 

Management of Bacterial Meningitis
General principle is that you need to start appropriate antibiotics ASAP.   If LP is going to be delayed by need for CT scan, obtain blood cultures and start Abxs right away.

Empiric therapy:

• Vancomycin --> for PCN-resistant S.pneumo, NOT for MRSA (unless you are worried about health-care associated meningitis)

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• Ceftriaxone – 2 g q12 hours – note the higher dosing (usually 1-2 g q24 hrs) -->for non-resistant S.pneumo, N.meningitidis, and H.influenza.  Do not forget to use the correct Ceftriaxone dosing otherwise you will look bad like the OSH doctors.

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• (Ampicillin – for all pts > 50 yo, immunocompromised, pregnant)

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• Dexamethasone 10 mg IV q6 hrs – per 2004 IDSA guidelines, start for all pts with suspected bacterial meningitis immediately prior to or with first dose of Abxs.  Basic idea is to decrease CNS inflammation which is worsened by Abx-mediated killing of bacteria (similar to rationale for steroids for severe PCP pneumonia).   Benefit is only definitively seen for S.pneumo meningitis, guidelines recommend to stop steroids if other bug is isolated (although this is somewhat controversial).  

 

 

 

Aseptic Meningitis:

• defined as evidence of meningitis with negative routine bacterial cultures
• Ddx includes viral vs. fungal vs. parasitic vs. atypical bacterial infections, autoimmune, drug-induced and malignancy
• Viral: enterovirus, coxsackie, HSV-2, HIV, LCMV, arboviruses, mumps (less commonly CMV, HSV-1, EBV, Herpes zoster)
• Atypical bacterial: TB, lyme disease, leptospirosis, parameningeal infxn (ie. epidural abscess), partially treated bacterial meningitis (less commonly ricketsia spp., mycoplamsa, chlamydia, brucella spp, erlichia spp)
• Fungal: crypto, cocci, histo
• Parasitic: toxoplasma
• Drugs: NSAIDs (esp ibuprofen), TMP-SMX, azathioprine, IVIG, anti CD3 ab (OKT3)
• Malignancy: lymphoma, leukemia, metastatic cancer
• Autoimmune: SLE, Behcet’s, Sarcoid
• Key is to distinguish bacterial meningitis from other (aseptic): both can have a similar initial clinical appearance, but in contrast to bacterial meningitis, most pts with aseptic meningitis have a self-limited course that will resolve even without specific therapy

 

Treatment of VZV Meningoencephalitis:
The current recommendation is for Aciclovir IV 10 mg/kg 3 times daily for one week
Duration may need extension in immunocompromised patients
Once CrCl < 50 mL/minute/1.73 m2, frequency reduced to BID

 

Acyclovir Toxicities:
Most common include Malaise, headache
GI upset, nausea, vomitting
LFT abnormalities
Acute renal failure
hives, itching and rash

 

 

Mollaret’s meningitis:

• Recurrent benign lymphocytic meningitis
• Defined as greater than three episodes of fever and meningismus lasting two to five days, followed by spontaneous resolution
• Most common etiology is HSV-2> HSV-1, but some cases have no clear etiology 

 

 

(Ellen Eaton MD, 2/10/11)

(Victoria Kelly MD, 10/7/10)

(Chanu Rhee MD, 10/11/10)