Authors: Aaron Tiffee, M. D. and Marc Zosky, D.O. (LSUHSC Baton Rouge Emergency Medicine Residency Program, Our Lady of the Lake Regional Medical Center) // Editor: Alex Koyfman, MD & Justin Bright, MD

It is another busy night in the ED. The patients are lining the halls on extra beds and three ambulance crews are impatiently waiting for the charge nurse to tell them where to put the 3 most recent incoming patients. You finally make it down to the your next patient: a 24 year-old male brought by his roommate because he “wasn’t acting right.” The roommate denies any previous episodes like this, a significant psychiatric history, or drug or alcohol use. He states that the patient was “like this when I got home.” He was last seen normal 24 hours ago. There has been no recent travel and no reported past medical or surgical history. Vital signs are: T-38°C, HR-104 bpm, RR-16 non-labored, SpO2 99% on room air. Physical exam reveals a confused and mildly agitated, ill-appearing male with equal and reactive pupils, supple neck, normal heart sounds without a murmur, lungs are clear to auscultation bilaterally, soft non-tender abdomen, no focal neurological deficits, and no skin or extremity abnormalities.

What is on your differential, what diseases are making their way to the top of your list, and what questions should you be asking yourself? A few of the questions in your mind should at least be: what is most likely to kill this patient, do I need to get a CT of the head, does he need a lumbar puncture, does he need any urgent medications, and what labs should I order?

This patient is definitely “sick” in the sick vs not sick dichotomy, as he is febrile, confused, and has abnormal vital signs. While he has no clear source of infection on initial presentation, somewhere high on your differential should be a central nervous system infection such as meningitis. A thorough physical and neurological exam is paramount in your decision making process at this point of the assessment. Meningeal disease should not be ruled out simply because patients do not present with the “classic triad” of fever, altered mental status, and stiff neck. A 1993 study of 493 patients with meningitis found that 95% had fever, 88% had neck stiffness, 78% had altered mental status.3 A more recent study reported that only 44% of patients with meningitis had all three components of the classic triad, but nearly every patient with meningitis has at least one of the symptoms.12 Neck pain offers only 28% sensitivity and headache only offers 50% sensitivity to meningitis. Furthermore; non-pulsatile and generalized headaches only offered specificities of 15% and 50%, respectively.1

Patients with meningitis can have a variety of symptoms, and your guard should never be lowered if they do not follow the classic textbook presentation… this is how people die in your ED. One important pitfall to avoid is minimizing afebrile patients. This is especially true in the elderly population, as many as 18% of these patients with meningeal infection may be afebrile.7 Other physical exam findings that are less common, but if present should also raise your suspicion, are focal neurological deficits, cranial nerve palsies, seizures, papilledema, non-blanching rash, and hearing loss (which is a very late sign).3

In medical school we were all taught the infamous Kernig and Brudzinski signs, and were practiced ad nauseam in our clinical medicine classes. The Kernig and Brudzinski signs have been shown to offer little to no help in diagnosing meningitis. Although there is a reported 95% specificity, the sensitivity is as low as 5%.9 These tests are antiquated, take up valuable time, and should have no real place in the evaluation of meningitis. The “jolt test” is a slightly more sensitive physical exam tool. This test is considered positive if the headache is accentuated by horizontal rotation of the head at a frequency of two to three times per second. But, studies of the jolt test produced variable sensitivities, ranging from 97%10 measured in 1991 to 21%8 in 2013 raising questions about its utility in diagnosing meningitis. Ultimately, outside of a positive CSF culture, no one test or exam should rule in or out the diagnosis of meningitis. A patient may or may not have all the aspects of the disease and we as clinicians have a duty to maintain that omnipotent high level of suspicion and clinical gestalt.

Another important aspect of your work-up is the diagnostic studies: blood work, radiology, and CSF analysis. Consider obtaining CBC, CMP, and PT/PTT in all patients. For patients that are particularly concerning, such as the one described in the vignette above, or those meeting criteria for systemic inflammatory response syndrome (SIRS), two sets of timed blood cultures should be obtained, a serum lactic acid level, as well as a chest x-ray and urinalysis to rule out other sources of infection. These patients should also have a lumbar puncture performed as rapidly as possible with an opening pressure recorded. Since an opening pressure is an essential aspect of the lumbar puncture results, the procedure needs to be performed with the patient in a lateral decubitus position rather than upright. An opening pressure greater than 20 cm/H2O should raise some concern. Again, a normal opening pressure does not always mean that the disease is not present. Patients with meningeal infections may have a wide range of opening pressures from normal to high. Evidence has shown that as many as 9% of patients with bacterial meningitis have been found to have opening pressures of less than 14 cm/H20.3 CSF fluid should be evaluated for cell count, protein, glucose, cultures, and bacterial antigen. In certain patients, antigens to HSV, West Nile or other viruses should be studied, as well as cryptococcal antigen in any immunocompromised patient. Gram stain of CSF can be a helpful tool in early identification of bacterial meningitis:

Gram positive diplococci = Streptococcus pneumoniae

Gram negative diplococci = Neisseria meningitidis

small pleomorphic Gram negative coccobacilli = Haemophilus influenzae

Gram positive rods and coccobacilli = Listeria monocytogenes

Gram negative rods = Escherichia coli

Lumbar puncture and CSF analysis should not be delayed by a CT of the brain in every patient. The current Infectious Disease Society of America (IDSA) Guidelines13 delineate which patients need a CT of the brain before LP:

focal neurologic deficit

abnormal level of consciousness

new-onset seizure within one week prior to presentation

papilledema

history of central nervous system disease (mass lesion, stroke, focal infection)

immunocompromised state (HIV, immunosuppressive therapy, solid organ or hematopoietic stem cell transplant)

The short of it… do not scan every patient’s head before LP unless they meet the criteria set forth by the IDSA. This cuts down on delay of diagnosis, health care cost, length of stay in the ED, and unnecessary exposure of our patients to radiation.

Another needless pitfall in managing patients with meningitis is delaying the administration of antibiotics, antivirals, or other potentially life-saving medications while waiting on the diagnosis to be confirmed. If the degree of suspicion is high, these medications should be administered without delay. This means initiating therapy prior to the LP! Patients who are suspected of having bacterial meningitis, should be prophylactically given a third generation cephalosporin, vancomycin, and in the infants, older populations (>50 years of age) or immunocompromised, ampicillin should be added for Listeria monocytogenes coverage.12 The administration of IV steroids has also been shown to improve patient outcomes. A 2007 Cochrane Review found a decrease in overall mortality in patients who received 0.15mg/kg of IV dexamethasone when given before or concomitantly with IV antibiotics, most particularly with Streptococcus pneumoniae infections (RR, 0.59; 95% CI, 0.45-0.77).11 Early administration of acyclovir for patients with HSV encephalitis has also been shown to decrease mortality from over 70% to around 30%.6

Close contacts of patients diagnosed with Neisseria meningitidis should always be prophylactically dosed with oral ciprofloxacin or rifampin. Rifampin is administered twice daily for 2 days (600 mg every 12 hours for adults, 10 mg/kg of body weight every 12 hours for children greater than or equal to 1 month of age, and 5 mg/kg every 12 hours for infants less than 1 month of age). Rifampin is not recommended for pregnant women, because the drug is teratogenic in laboratory animals. A single 500-mg oral dose of ciprofloxacin is a reasonable alternative to the multi-dose rifampin regimen.2 The Centers for Disease Control and Prevention defines close contacts as:

household contacts

day care contacts

intimate non-household contacts

health care contacts with direct mucosal contact with the patient’s secretions (i.e. intubation or respiratory suctioning)

Once a patient has had twenty-four hours of effective antibiotic therapy they are essentially noninfectious and health care workers and family members that come into contact with the patient after this point do not need to be treated. Close contacts do not need to be treated for patients diagnosed with Haemophilus influenzae, Streptococcus pneumoniae, Listeria monocytogenes, Cryptococcal meningitis, viral (aseptic) meningitis, or West Nile Encephalitis.2

Summary of Pitfalls to Avoid

Assuming that a patient does not have meningitis because they do not have all components of the classic triad: fever, altered mental status, and neck stiffness

Lowering your index of suspicion in afebrile elderly patients

Solely relying on the physical exam, and special tests including the Kernig, Brudzinski or Jolt test to rule in or out the diagnosis

Delaying lumbar puncture to obtain a CT by failing to follow the IDSA criteria for CT exam prior to LP

Delaying the administration of appropriate IV antibiotics, antivirals, or steroids.

Failure to prophylactically treat close contacts of patients with Neisseria meningitidis

Meningitis is a debilitating disease with high morbidity, mortality, and long-lasting neurological sequelae. You must maintain a high index of suspicion and not rely on one single exam or test to rule in or out the diagnosis of meningitis. As an Emergency Medicine physician you must utilize a variety of physical exam techniques, diagnostic studies, and avoid the common pitfalls listed in this article. Our responsibility as clinicians is to quickly identify these patients and more importantly deliver rapid and timely therapy.

References / Further reading:

Attia J., Hatala R., Cook D.J., Wong J.G. “The rational clinical examination: Does this adult patient have acute meningitis?” JAMA1999;282:175-81. CDC website. “Control and Prevention of Meningococcal Disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP)” http://www.cdc.gov/mmwr/preview/mmwrhtml/00046263.htm. Accessed 12/8/2014 Durand ML, Calderwood SB, Weber DG, et al. “Acute bacterial meningitis is adults. A review of 493 episodes.” N Engl J Med1993; 328:21. Kaplan SL. Clinical presentations, diagnosis, and prognostic factors of bacterial meningitis. Infect Dis Clin North Am 1999; 13:579. Nakao JH, Jafri FN, Shah K, Newman DH.” Jolt accentuation of headache and other clinical signs: poor predictors of meningitis in adults”. Am J Emerg Med2014; 32:24 McGrath N, Anderson N, Croxson M, Powell K. “Herpes simplex encephalitis treated with acyclovir: diagnosis and long term outcome.” J Neurol Neurosurg Psychiatry. 1997 September; 63(3): 321–326. Shak K, Richard K, Edlow JA. “Utility of lumbar puncture in the afebrile vs febrile elderly patient with altered mental status: a pilot study”. J Emerg Med. 2007;32 (1): 15-18 Tamune H, Takeya H, Suzuki W, et al. “Absence of jolt accentuation of headache cannot accurately rule out meningitis in adults”. Am J Emerg Med 2013; 31:1601. Thomas KE, Hasbun R, Jekel J, Quagliarello VJ. “The diagnostic accuracy of Kernig’s sign, Brudzinski’s sign, and nuchal rigidity in adults with suspected meningitis.”Clin Infect Dis. 2002;35(1):46-52. Uchihara T, Tsukagoshi H. “Jolt accentuation of headache: the most sensitive sign of CSF pleocytosis. Headache” 1991; 31:167 van de Beek D, de Gans J, McIntyre P, Prasad K. “Corticosteroids for acute bacterial meningitis” Cochrane Database Syst Rev. 2007;(1):CD00405. van de Beek D, de Gans J, Spanjaard L, et al. “Clinical features and prognostic factors in adults with bacterial meningitis” N Engl J Med2004; 351:1849 Tunkel, A, Hartman, B, et al. “Practice Guidelines for the Management of Bacterial Meningitis” Clinical Infectious Diseases ; 2004 ; 39 : 1267 -1284 http://www.ncbi.nlm.nih.gov/pubmed/25441043 http://www.ncbi.nlm.nih.gov/pubmed/24188604 http://www.ncbi.nlm.nih.gov/pubmed/23910166