Leung, Anthony K. DO
Department of Internal Medicine, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown; and Infectious Disease Service, Summa Health System, Akron, OH.
Address correspondence and reprint requests to Anthony K. Leung, DO, Summa Physicians Infectious Disease, 75 Arch St, Suite 105, Akron, OH 44304. E-mail: firstname.lastname@example.org.
Acute adult meningitis remains a medical emergency, especially in cases of bacterial meningitis. Before the preantibiotic era, the mortality of pneumococcal meningitis was virtually 100%. With the implementation of aggressive childhood vaccinations, specifically vaccines against Hemophilus influenza type b and Streptococcus pneumoniae; there is an overall decline of diseases caused by these organisms.1,2 The diagnosis and management require a multidisciplinary approach. The 3 most common bacterial pathogens are S. pneumoniae (most common), H. influenza, and Neisseria meningitides.3-7 Studies have shown that a delay in diagnosis and treatment will often lead to dire consequences ranging from hearing loss, cognitive impairment, and death.8-11
Diagnosing acute adult meningitis has been a challenge especially for emergency department (ED) physicians. Recently, the issues involving the management of suspected cases of acute meningitis were reviewed extensively.12,13 The Infectious Disease Society of America has also published guidelines in managing bacterial meningitis.14 The core work-up and management for such cases are fundamentally composed of the following components: a detailed history and physical examination, imaging of the central nervous system in selected high-risk patients (computed tomography and magnetic resonance imaging), lumbar puncture (LP) for cerebrospinal fluid (CSF) analysis, and administration of appropriate antimicrobial agents.
Literature has suggested that symptoms, signs, and to a certain extent physical examination are not that reliable to distinguish and ascertain which patients truly have meningitis. In the fast-paced ED setting, many subjective complaints and symptoms could be elicited from patients; however, it is often difficult to sort out which ones are significant and not just "red herring." The clinician's initial impression and assessment of the patient are true keys for obtaining an appropriate work-up. However, a patient's symptoms alone are generally not reliable for sorting out which patients do have symptoms of acute meningitis and which patients do not. Attia et al15 conducted a meta-analysis that pooled 10 studies with a total population of 824 patients aged from 16 to 95 years. The studies found that symptoms such as headache and nausea/vomiting only had a sensitivity of 50% and 30%, respectively. In suspected cases, additional technique might increase sensitivity. Jolt accentuation of headache is performed by turning the patient's head horizontally 2 to 3 seconds per second. The test result is positive if the patient experiences worsening of baseline headache. This maneuver when used in patients with headache and fever could potentially increase the sensitivity to 100% and specificity to 54%. However, the most striking finding was that in the absence of fever, neck stiffness, and altered mental status, one could essentially eliminate meningitis with a high level of confidence (sensitivity, 99%-100%).15
Because the history may not be helpful in ascertaining the diagnosis, physical examination and certain physical signs, in theory, might add additional clues. In classic teaching, medical students and residents are taught the Kernig sign, Brudzinski sign, and meningismus. Interestingly, the Kernig sign was originally described by a Yugoslavian physician named Lazarevice who never received credit. Both signs basically demonstrate meningeal irritation by maneuvering either the legs (Kernig sign) or the neck (Brudzinski sign). Recent studies have shown that both signs have poor sensitivity and specificity. Thomas et al16 studied 297 adult patients with suspected meningitis. The sensitivity of Kernig sign, Brudzinski sign, and nuchal rigidity were 5%, 5%, and 30%, respectively.16 It was concluded that these classic physical examination signs did not have diagnostic value.
To properly diagnose meningitis, the work-up must consist of a combination of clinical and laboratory diagnosis including the LP, which is a key component. Generally, clinicians could readily raise the suspicion of meningitis by examining CSF white blood cell count, protein level, glucose level, and gram stain. Differentials of white blood cell counts could provide clues to differentiate between bacterial and viral meningitis. The predominance of polymorphonuclear leukocytes in CSF cell count differentials, high protein level, hypoglycorrahachia, and gram-positive stain can rule in bacterial meningitis with high degree of confidence.17 However, the challenge from an ED physician's perspective is that there are no clinical or published guidelines to reliably distinguish which patients will require an LP.
Within this issue of Infectious Diseases in Clinical Practice, Scott and colleagues conducted a retrospective study to examine this question. The study reviewed electronic medical records spanning an 8-month period (late spring to early fall) and identified 164 LPs performed during this time frame. Theoretically, the breadth of this period could potentially include some seasonal meningitis (such as Enterovirus). The incidence of confirmed cases of meningitis during the study period was fairly low at 6.7% (11 patients); and only 3 of these cases were confirmed as bacterial. There were only 6 cases of viral meningitis, in which 3 might have warranted treatment (2 cases of herpes simplex virus and 1 case of varicella zoster virus). The pathogen of 1 of the 3 bacterial cases was a coagulase-negative Staphylococcus, and whether there was presence of a foreign body (such as a shunt) and the clinical significance of this organism were not known.
This was an interesting study and once again reinforced the concepts that the diagnosis of meningitis remains challenging. A patient's history and examination cannot inclusively or exclusively rule out meningitis. Examination of CSF is still critical in diagnosing meningitis. The limitations of the study were described by the authors. This study, being a retrospective electronic chart review, would inherently incorporate confounding variables and bias, and one could not ascertain certain recorded physical signs and symptoms. As pointed out by the authors, 27 of the patients received antibiotics prior to LP, and that could have affected the yield of the culture. From a clinician's perspective, the timely administration of appropriate therapy, especially in such cases, is crucial. Some data from a retrospective study have shown that administration of antimicrobials in the ED could decrease the mortality rate from 29% to 7.9% compared with the administration of antimicrobials in inpatients.18 This is a significant issue because prospective data have shown that by delaying the administration of antimicrobials for more than 3 hours, in cases of pneumococcal meningitis, the 3-month mortality rate in those patients was higher.11 One could speculate that if history, examination, and laboratory studies suggest a case of meningitis, specifically bacterial meningitis, therapy would be initiated in the ED. Administration of antimicrobials might also sterilize CSF before obtaining LPs. Kanegaye et al19 reviewed records of 128 pediatric patients retrospectively. It was noted that CSF sterilization could be achieved in 2 hours for meningococcal meningitis and 4 hours for pneumococcal meningitis.19 These factors might have contributed to the low rate of the "usual" bacterial pathogens. However, the attack rate of this cohort was quite low, and therefore the administration of antibiotics before LP was not significant.
Another interesting point in this study was that 11.6% of studied patients were infected with human immunodeficiency virus (HIV), whereas there were only 2 cases of meningitis associated with HIV infection (1 case each of Cryptococcus neoformans and Treponema pallidum). It was unclear whether this frequency reflected the actual individual patients or if the same patients were recorded more than once. Either way in this cohort, the low incidence of opportunistic central nervous system infections suggested that the population with HIV infection was relatively stable and not a factor in this study.
Overall, this was an interesting study as many of these cases were presented first in the ED. It illustrated once again that it is a difficult task to ascertain the diagnosis without pursuing an LP. The classic triad of headache, nuchal rigidity, and altered mental status by themselves is neither inclusive nor exclusive of such a diagnosis. Statistically, the significant findings of this study required CSF sampling, and therefore LPs remain the key component of diagnostic work-up. Certainly, more studies are needed to better use LPs in the ED environment. In this study, patients who had LPs done stayed an average of more than 4 hours longer in the ED than did those who did not. However, given the seriousness of meningitis especially among bacterial cases, LPs should be performed as long as it is clinically indicated.
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