A 3-year-old boy has had a normal developmental history since birth. Both of his parents work, so he has been attending the same day care center for two years. He has had several episodes of presumed viral infections similar to those seen in other children at the day care center and has recovered from all of them. His childhood immunizations are current. The boy suddenly develops fever and loss of appetite. These symptoms persist for about a day, at which point the boy's parents begin to find it hard to arouse him. Alarmed by this new development, they take the boy to the nearest emergency room for treatment.

The boy's vital signs are: T = 39.5ºC, P = 130, R = 25, and BP = 110/60 mm Hg. On physical examination, the boy is found to be well-developed and well-nourished. He is somnolent and, when his neck is passively flexed, his legs also flex. An ophthalmoscopic examination fails to detect any signs of papilledema. There are no other remarkable physical findings.

Question 1.1: What is your preliminary diagnosis?

The positive Brudzinski sign (flexing of legs when neck is passively flexed) can indicate inflammation of the meninges (meningitis) and is perhaps the most instructive sign in this case. Fever, loss of appetite, and lethargy are also consistent with a diagnosis of meningitis (which appears to be acute, given that the symptoms have developed in only 24 hours). More than 90% of meningitis cases produce the classic combination of fever, headache, and nuchal rigidity ("stiff neck"). Alteration in mental status, which may range from sleepiness to coma, occurs in >75% of cases. Nausea, vomiting, and photophobia are also common, but they do not appear as frequently as the above symptoms. Seizures occur as part of the initial presentation or during the course of the illness in about 40% of patients.

Question 1.2: What is the differential?

Depending on the signs and symptoms that actually present in a particular case of meningitis, the differential could include endocarditis with bacteremia, intracranial tumor, Lyme disease, a brain abscess, seizures, acute mononucleosis, neuroleptic malignant syndrome, Rocky Mountain spotted fever, subdural empyema, and reactions to certain medications.

Question 1.3: What tests should you perform?

If your preliminary diagnosis is correct, this is an emergency situation and you must confirm the diagnosis as quickly as possible. The top priority (after having confirmed that the patient has no signs of papilledema) is a lumbar puncture. Opening pressure should be measured, and samples of CSF should be taken for culturing, cell counts, chemical analyses, and Gram stains. Other potentially useful tests would include a CBC with differential and blood cultures.

Test Results:

The opening pressure during the lumbar puncture was 350 mm of CSF, and the fluid was cloudy. A Gram stain of the CSF (which was carried out immediately after obtaining the fluid) revealed many PMNs with intracellular Gram-negative diplococci. Blood chemistry tests were normal, as was the hematocrit. The WBC count was 25,000/microliter, with 80% PMNs, 8% bands, 6% lymphocytes and 6% monocytes. The absolute neutrophil count was 22,000/microliter. The CSF contained 5,000 WBC/microliter, of which 99% were neutrophils. The CSF protein was 100 mg/dL (normal up to 45) and CSF glucose was 15 mg/dL (serum glucose 79 mg/dL). Cultures of blood and CSF grew a Gram-negative diplococcus.

Question 1.4: What is the likely causative agent?

60% of acute meningitis cases in persons between 2 and 20 years of age are caused by Neisseria meningitidis, which would be consistent with the Gram-stain and culture findings obtained in this case. (In fact, the lab eventually confirmed that N. meningitis as the causative agent.) The most frequent causative agent of acute bacterial meningitis varies with different age groups. Streptococcus agalactiae is the most frequent cause in infants up to the age of 2 months, while Haemophilus influenzae is slightly more common than Neisseria meningitidis in patients aged 2 months to 2 years. In contrast, Streptococcus pneumoniae is the most frequent cause of acute meningitis in patients over 20 years old. Other significant causative agents include Listeria monocytogenes and Escherichia coli. Haemophilus influenzae type b was once a leading cause of acute meningitis in the U.S. but has become relatively unimportant since the introduction of the vaccine in the 1980s.

Question 1.5: How did this disease come about?

The child was most likely infected at his day care center, either via respiratory droplets in the air or through direct contact (e.g., transfer of respiratory secretions from hand to hand). The source of infection may have been an asymptomatic carrier. (Obviously, the day care center should be notified and the children attending it should receive a prophylactic dose of antibiotics.) The bacteria colonized the mucosal surfaces in the boy's nasopharynx by using pili to adhere to nonciliated columnar cells. The bacteria were then internalized into phagocytic vacuoles and because they could avoid intracellular death, they migrated to the subepithelial spaces, entered the bloodstream, and eventually made their way into the CNS.

Question 1.6: How should you treat this case?

Antibiotic therapy should be initiated immediately. In this case, the boy was started on intravenous cefotaxime therapy within 40 minutes of his arrival at the ER. Dexamethasone (a steroid) was also given, to reduce inflammation. Antibiotic treatment was continued for 14 days, and the boy recovered with no obvious sequelae. Rifampin prophylaxis was given to the other children who attended his day care center. The most appropriate treatment regimen for any specific case of acute meningitis depends on the identity of the causative agent, the age and medical condition of the patient, and the circumstances that led to their infection. Persons with a meningococcal infection can die within a day of the first onset of symptoms.