Central Nervous System Infections

Meningitis is an inflammatory process of the meninges. It’s that straightforward. While we worry most about bacterial meningitis, the most common form of meningitis is actually “aseptic” meningitis, which is the term used when CSF bacterial cultures are negative. As you would expect, most aseptic meningitis cases are due to viruses—typically enteroviruses, HSV-2 (commonly in association with primary infection, so patients tend to have genital lesions) and arboviruses. (Remember, HSV-1 is associated with encephalitis that has a predisposition for the temporal lobes; HSV-2 is associated with meningitis.) Unless the patient has underlying herpes infection, viral meningitis is managed supportively. Typically, these patients receive empiric antibiotics only until CSF cultures exclude bacterial meningitis.

When it comes to bacterial meningitis, the most common pathogen is Streptococcus pneumoniae (>70% of cases) followed by Neisseria meningiditis, Haemophilus influenzae, Group B Streptococcus, and Listeria monocytogenes. (In patients who have had neurosurgery, CNS prosthetic device placement, or bacteremia, Staph aureus is also a consideration.)

See the table below for some quick factoids about each, listed in order of frequency. Conveniently, these organisms are easy to distinguish on CSF gram stain and so knowing just a little bit of microbiology can help you diagnose your patients!

[Images from CDC, ASM Microbe Library and LabMedicineBlog.]

In general, the symptoms of meningitis are the same whether it’s a bacterial or viral process. Patients will have fever, headache, neck stiffness, and/or photophobia. Physical exam maneuvers like the Kernig and Brudzinksi signs are not very sensitive or specific; the jolt accentuation test (i.e., worsening of headache by horizontal rotation of the head 2-3 times per second) is also not reliable to rule out meningitis (mixed data, specificity between 40-80%). Because of this, blood cultures should be obtained immediately, and every effort should be made to obtain CSF for analysis as soon as is safe.

Prior to LP, consider whether a head CT is indicated. If there are signs or symptoms of increased intracranial pressure (papilledema, CNS mass lesion, stroke), focal neurologic deficits or altered mental status—get a head CT first. Also check a head CT if the patient is immunocompromised (HIV or on immunosuppressive therapy). If your patient has none of the above, proceed to LP without imaging.

You’ve all been forced to memorize the typical CSF findings in patients with viral versus bacterial meningitis (see table 2 below) but in general, just remember that bacterial processes are more inflammatory: the opening pressure will be >20 cm H2O, you’ll have a high CSF WBC count (>1000, with neutrophilic predominance), low glucose <40 (glucose will be depleted for bacterial cellular respiration), and high protein >200. That being said, the spectrum of CSF values in bacterial meningitis is very wide, so the absence of one or more of these findings is of little consequence.

Right after LP is performed and CSF has been collected, start empiric antibiotics and adjunctive dexamethasone.

Why dexamethasone?

Unfortunately, permanent neurologic sequelae, such as hearing loss and focal neurologic deficits, are known to occur in survivors of bacterial meningitis, especially those with pneumococcal infection. In fact, some experts believe that Helen Keller’s deafness was due to childhood bacterial meningitis with Neisseria or Haemophilus! The good news is that steroids have been shown to improve morbidity in patients with bacterial meningitis in developed countries. Adjunctive dexamethasone is given for 4 days only, and it is recommended to be administered prior to or with the first dose of antibiotic therapy in any patient with suspected bacterial meningitis. It is reasonable to discontinue steroids if pneumococcus is ruled out. (That is, no gram-positive cocci seen on CSF gram stain and CSF/blood cultures do not grow Strep pneumo.)

So, your empiric antibiotic + steroid cocktail in a patient without nosocomial risk factors should include:

1)      Ceftriaxone 2g IV q12h (to cover Strep pneumo, H. influenzae and Neisseria meningitidis) and

2)      Vancomycin IV, goal trough 15-20  and

3)      Dexamethasone 0.15 mg/kg IV q6h (15 min prior to or with the first dose of antibiotic therapy) and possibly

4)      Ampicillin 2g IV q4h (to cover Listeria in the elderly or immunosuppressed patient)

*For patients with a history of neurosurgical procedures, or if there is concern for hospital-acquired bacterial meningitis: start vancomycin IV (for coverage of Staph aureus, including MRSA) as well as cefepime 2g IV q8h (for coverage of gram-negative organisms such as Pseudomonas.) There is minimal data on the penetration of pip-tazo (Zosyn) into the CNS, so avoid pip-tazo for CNS infections!

 To summarize:

1)      If you suspect bacterial meningitis, get blood cultures emergently.

2)      Determine if your patient needs a head CT prior to LP. Following LP, start empiric antibiotics (vancomycin IV + ceftriaxone IV +/- ampicillin IV) and dexamethasone.

3)      Follow up cultures, CSF findings and tailor antibiotic therapy as needed.

Extra nerdy: Look up Mollaret meningitis if you’re bored—it’s a rare, benign lymphocytic meningitis associated with HSV-2 that recurs weeks to years apart.