Heady

Nervous System & Special Senses

Diagnosis and reasoning

This elderly man has presented with a high fever, severe headache, and photophobia. This should be considered a central
nervous system (CNS) infection until proven otherwise.

Key diagnoses to consider include meningitis, encephalitis, or a cerebral abscess. If these are excluded, the possibility of a
subarachnoid hemorrhage (SAH) should be kept in the back of the mind.

Encephalitis is usually associated with focal signs and cognitive deficits, while headache is o en not the primary feature.
Cerebral abscesses tend to have a more subacute presentation.

Conversely, the headache of bacterial meningitis is typically acute in onset, reaching maximal severity over a few minutes or
hours; it is usually generalized, severe and unremitting, as seen here.

The examination shows him to be confused and lethargic, with a subnormal GCS score. At first glance, the absence of nuchal
rigidity and negative Kernig and Brudzinski signs seem to argue against meningitis. However, the jolt accentuation test is
positive.

Note that the Kernig and Brudzinski signs are only about 23% and 28% sensitive for meningitis respectively, while neck sti ness
is only 30% sensitive. Jolt accentuation is 50% sensitive and 71% specific for meningitis.

A lumbar puncture is a suitable next step. Preceding computed tomography (CT) to exclude mass lesions is now only
recommended in patients with a GCS <12, or if papilledema or focal neurological signs are present.

Cerebrospinal fluid analysis (CSF) reveals several useful clues: elevated protein levels, a marked neutrophil leukocytosis, a CSF
glucose to serum glucose ratio of ~0.18, and most importantly, gram positive rods.

These findings are diagnostic of bacterial meningitis; when the patient's age and the gram stain results are considered, Listeria
monocytogenes ranks topmost among the list of possible etiological agents.

Note that magnetic resonance imaging (MRI) of the brain is not indicated currently, as it is unlikely to reveal any additional
information of diagnostic or prognostic value.

Blood cultures should be obtained and empirical antibiotics started a erwards. Ampicillin is the drug of choice in suspected
Listeria meningitis. While the addition of gentamicin can be synergistic, detrimental side-e ects may occur. In particular, there is
conflicting evidence about the use of aminoglycosides in the elderly.

Current guidelines recommend that corticosteroids be commenced before or along with antibiotics. Starting them a er
antimicrobial therapy is unlikely to improve outcomes. If corticosteroids are commenced empirically and Listeria meningitis is
confirmed a erwards, they should be discontinued.

Respiratory isolation and chemoprophylaxis of close contacts is not indicated, as Listeria is spread via the gastrointestinal route.

Discussion
Meningitis is defined as inflammation of the pia and arachnoid layers of the meninges; it is most o en secondary to bacterial or
viral infection. In the USA, meningitis accounts for 72,000 hospitalizations and $1.2 billion in hospital costs annually. The
incidence ranges from 1.3 to 2 per 100,000 individuals per year.

The remainder of this monograph pertains to community-acquired bacterial meningitis in adults. However, much of the
information is also applicable to hospital-acquired disease.
The key pathogens implicated in community-acquired meningitis are N. meningitidis, S. pneumoniae, Listeria spp, and rarely,
gram-negative bacteria. While H. influenzae was an important cause in earlier decades, the number of cases decreased
dramatically a er the advent of the Hib vaccine.

Meningitis typically begins with an initial episode of bacteremia. In the case of meningococci and pneumococci, this is
subsequent to invasion of the nasopharyngeal mucosa. With Listeria spp. and gram negative organisms, the gastrointestinal (GI)
tract is the usual entry point.

Once in the subarachnoid space, the infecting bacteria elicit a severe inflammatory response. This can extend along the blood
vessels and proceed deep into the brain parenchyma, causing complications such as cerebral edema, hydrocephalus, and stroke.

Classically, meningitis has been identified by the triad of fever, neck sti ness, and altered mental status. Other findings generally
described include headache, photophobia, nausea and vomiting, focal neurological signs, and the Kernig and Brudzinski signs.
These can develop within hours to days.

Unfortunately, the classical triad is of limited sensitivity. In one study, it was seen in only 46% of patients. The Kernig and
Brudzinski signs are also of poor sensitivity, i.e., 23% and 28% respectively.

The jolt accentuation test is an alternative clinical test, with ~50% sensitivity and 71% specificity. This is performed by asking a
patient with a headache to quickly move their head twice horizontally. Worsening of the headache constitutes a positive test.

The presence of certain symptoms and signs can also point towards the likely etiology. For example, S. pneumoniae is more
probable in patients who do not have a spleen, or with a primary or secondary immunoglobulin deficiency (including multiple
myeloma and HIV infection).

Furthermore, N. meningitidis is associated with crowding (e.g., dormitories), while patients with certain complement
deficiencies are at increased risk of infection; and, 60% of adults with meningococcal meningitis develop a petechial rash with
thrombocytopenia.

Recent consumption of contaminated food such as raw vegetables, unpasteurized milk and cheese, and deli meats should raise
concern of Listeria infection.

Lumbar punctures are key to diagnosing meningitis, and determining the likely etiological agent. Cerebrospinal fluid (CSF)
specimens should be sent for culture as soon as possible.

In acute bacterial meningitis, the opening pressure is usually elevated (>18 cmH2O). CSF protein levels are elevated, and glucose
levels reduced, while the leukocyte count is o en >1.0 x 10^9/L, with a predominant neutrophilia.

Interestingly, a CSF glucose to serum glucose ratio of <0.4 is a better predictor for bacterial meningitis than all of the above.
Furthermore, if CSF lactate levels are measured, a value >31.5 mg/dL (>3.5 mmol/L) is predictive of meningitis, while a lower level
makes the diagnosis unlikely.

Gram staining of the CSF is also a useful tool. If bacteria are seen, it is almost 100% specific for meningitis. However, a negative
result does not rule out the possibility.

Note that lumbar punctures should be performed before initiation of antibiotics. Studies have shown that sterilization of the CSF
occurs a er only a few hours. However, where lumbar punctures cannot be performed on a timely basis, antibiotic therapy
should never be delayed.

Blood cultures should also be drawn before antibiotics are started; however, they are positive only 19% to 70% of the time.

Note that current guidelines recommend CT neuroimaging prior to lumbar puncture only in patients with either a GCS <12,
papilledema, or focal neurological signs. However, if at least one of these is present, blood cultures should be obtained first,
empirical antibiotics started, and only a erwards should a CT scan be performed.

While the recommended empirical antibiotics vary by geographic region and hospital policy, intravenous (IV) third-generation
cephalosporins are a common first-line option. If drug-resistant pneumococcal strains are present, vancomycin can be added;
furthermore, in patients who are over 50 years of age, or immunocompromised, IV ampicillin can be added, so as to cover Listeria
spp.
Note that as gram stain results and culture reports become available, antibiotic therapy should be tailored appropriately.

The use of glucocorticoids is also a topic which has been studied, as many of the deleterious e ects of bacterial meningitis are
secondary to the profuse inflammatory response.

Current IDSA guidelines recommend that in adults with suspected or proven pneumococcal meningitis, dexamethasone should
be commenced; this is based on evidence from a Cochrane meta-analysis. However, there is limited and conflicting evidence of
their e icacy (or lack of it) in meningitis due to other organisms; use in this context is dependent on individual clinical discretion
and unit policy.

Note that corticosteroids should be commenced just before or in conjunction with antibiotic therapy; this will help diminish the
inflammatory response which may occur during treatment.

The timing of antibiotic therapy is the factor most closely associated with survival. Retrospective studies have shown that if
antibiotics are started within 6 hours of presentation the mortality rate is as low as 5% to 6%; if delayed to 8 to 10 hours from
presentation, this rises to as high as 75%.

Take home messages

1. Most classical signs and symptoms are of poor sensitivity for bacterial meningitis.
2. Not all patients need neuroimaging before a lumbar puncture. If required, antibiotics should be commenced beforehand.
3. The time antibiotics are first started directly a ects the resultant mortality of these individuals.
4. Glucocorticoids are beneficial in pneumococcal disease, but are unproven in meningitis due to other pathogens.

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