CASE A 20-year-old college student is your next patient in the emergency room. When you walk into the room, he is lying on the examination table, on his side, with his arm covering his eyes. The light in the room is off. You look at his chart and see that the nurse recorded his temperature as 102.3°F, heart rate 110 bpm, and blood pressure 120/80 mm Hg. When you gently ask how he has been feeling, he says that for the past 3 days he has had fever, body aches, and a progressively worsening headache. The light hurts his eyes and he is nauseated, but he has not vomited. He has had some rhinorrhea, but no diarrhea, cough, or nasal congestion. He has no known ill contacts. On examination, he has no skin rash, but his pupils are difficult to assess because of photophobia. Ears and oropharynx are normal. Heart, lung, and abdomen examinations are normal. Neurologic examination reveals no focal neurologic deficits, but passive flexion of his neck worsens his headache, and he is unable to touch his chin to his chest.
#What condition are you concerned about?
#What diagnostic test would confirm the diagnosis?
Summary: A 20-year-old college student presents with a 3-day history of fever, headache, myalgias, and nausea. He has no respiratory or gastrointestinal symptoms, but now has developed photophobia. He is febrile to 102.3°F, tachycardic, and normotensive. His physical examination is generally unremarkable with a nonfocal neurologic examination but some neck stiffness, suggesting meningeal irritation. He has no skin lesions as might be seen in meningococcemia.
#Most likely condition: Meningitis.
#Diagnostic test to confirm diagnosis: Lumbar puncture (LP) for evaluation of the cerebrospinal fluid (CSF), possibly preceded by a computed tomographic (CT) scan of the head.
ANALYSIS
Considerations This 20-year-old college student has headache, nausea, photophobia, fever, and neck pain and stiffness—all suggestive of meningitis, which could be bacterial or viral. Prompt LP and analysis of CSF are essential to establish the diagnosis. In a patient without focal neurologic signs and a normal level of consciousness, CT scan may be unnecessary prior to performing an LP. If he had a purpuric skin rash, one would be suspicious of Neisseriameningitis, and appropriate antibiotics should be administered immediately. Dosing of antibiotics in suspected meningococcal infection should not await the performance of any diagnostic test because progression of the disease is rapid, and mortality and morbidity are extremely high even when antibiotics are given in a timely manner.
DEFINITIONS
MENINGITIS:A serious inflammation of the meninges, the thin, membranous covering of the brain and the spinal cord, which can be caused by bacteria, viruses, fungi, or protozoa.
PAPILLEDEMA: Swelling of the optic nerve, caused by an increased intracranial pressure. On fundoscopic examination, the optic disc margin appears hazy.
CLINICAL APPROACH
Bacterial meningitis is the most common pus-forming intracranial infection, with an incidence of 2.5 per 10,000 persons. The microbiology of the disease has changed somewhat since the introduction of the Haemophilus influenzae type B vaccine in the 1980s. Now Streptococcus pneumoniaeis the most common bacterial isolate, with Neisseria meningitidisa close second.Group B streptococcusorStreptococcus agalactiaeoccurs in approximately 10% of cases, more frequently in neonates or in patients older than 50 years or with chronic illnesses such as diabetes or liver disease. Listeria monocytogenesaccounts for approximately 10% of cases and must be considered in pregnant women, the elderly, or patients with impaired cell-mediated immunity such as AIDS (acquired immunodeficiency syndrome) patients. Haemophilus influenzaeis responsible for less than 10% of meningitis cases. Resistance to penicillin and some cephalosporins is now of great concern in the treatment of S pneumoniae.
Bacteria usually seed the meninges hematogenously after colonizing and invading the nasal or oropharyngeal mucosa. Occasionally, bacteria directly invade the intracranial space from a site of abscess formation in the middle ear or sinuses. The gravity and rapidity of progression of disease depend upon both host defense and organism virulence characteristics. For example, patients with defects in the complement cascade are more susceptible to invasive meningococcal disease. Patients with CSF rhinorrhea caused by trauma or postsurgical changes may also be more susceptible to bacterial invasion. Staphylococcus aureusandStaphylococcus epidermidisare common causes of meningitis in patients following neurologic proceduressuch as placement ofventriculoperitoneal shunts. The brisk host inflammatory response in the subarachnoid space may cause edema, vasculitis, and coagulation of vessels, leading to severe neurologic complications including seizures, increased intracranial pressure, and stroke. Acute bacterial meningitis can progress over hours to days. Typical symptoms include fever, neck stiffness, and headache.Patients may also complain of photophobia, nausea and vomiting, and more nonspecific constitutional symptoms. Approximately 75% of patients will experience some confusion or altered level of consciousness. Forty percent may experience seizures during the course of their illness.
Some physical examination findings may be useful in the evaluation of a patient with suspected meningitis. Nuchal rigidityis demonstrated when passive or active flexion of the neck results in an inability to touch the chin to the chest. Classic tests include Kernig and Brudzinski signs. Kernig signcan be elicited with the patient on his or her back. The hip and knees are flexed. The knee is then passively extended, and the test is positive if this maneuver elicits pain. Brudzinski signis positive if the supine patient flexes the knees and hips when the neck is passively flexed. Neither sign is very sensitive for the presence of meningeal irritation, but, if present, both are highly specific. Papilledema, if present, would indicate increased intracranial pressure, and focal neurologic signs or altered level of consciousness or seizures may reflect ischemia of the cerebral vasculature or focal suppuration.
Differential Diagnosis
The differential diagnosis of bacterial meningitis is fairly limited and can be narrowed depending upon the patient’s age, as discussed earlier, exposure history, and course of illness. Various viral infections may also cause meningitis. These include enteroviruses, which tend to be more common in the summer and fall, when patients may present with severe headache, accompanied by symptoms of gastroenteritis. The CSF white blood cell (WBC) count will be elevated, with a predominance of lymphocytes, and usually glucose and protein levels are normal (Table 29–1). Either herpes simplex virus (HSV)-1 or HSV-2 can cause herpes simplex meningitis. The CSF of these patients will also have a normal glucose level, whereas protein and WBC counts will be elevated with a predominance of lymphocytes. Typically, these patients have a high CSF red blood cell count, which is not seen in bacterial meningitis in the absence of a traumatic spinal tap. In a patient with human immunodeficiency virus (HIV) infection, fungal meningitis, specifically caused by Cryptococcus, should be considered. Tuberculous meningitis presents subacutely and is more common in older, debilitated patients, or in patients with HIV. Rickettsial disease, specifically Rocky Mountain spotted fever, may also present with meningitis. Intracranial empyema, or brain or epidural abscess, should be considered, especially if the patient has focal neurologic findings. The one nonsuppurative diagnosis in the differential is subarachnoid hemorrhage. These patients present with sudden onset of the “worst headache of their lives” in the absence of other symptoms of infection. They may have photophobia, and the CSF will be grossly bloody; the supernatant will be xanthochromic, reflecting the breakdown of blood into bilirubin.
The necessity of imaging of the head and brain prior to performing an LP is controversial. Studies show that in the patient with suspected meningitis who does not have papilledema, focal neurologic signs, or altered level of consciousness, an LP may be safely performed without preceding imaging. However, in instances in which performance of the LP may be delayed, antibiotics should be administered after blood cultures while awaiting the radiologic studies. Ideally, the CSF should be examined within 30 minutes of antibiotics, but it has been shown that if the LP is performed within 2 hours of antibiotic administration, it will not significantly alter the CSF protein, glucose, or WBC count, or Gram stain. If CSF is obtained, a culture and Gram stain should be sent. If enough fluid is available, it should also be sent for cell count and glucose and protein levels. Latex agglutination tests for S pneumoniae andH influenzaecan be useful in patients pretreated with antibiotics, and, although not very sensitive, if positive they can rule in disease (high specificity). Polymerase chain reaction (PCR) testing is available for some bacteria; however, it may be more useful in the diagnosis of herpes simplex, enteroviral, or tuberculous meningitis. In all, no more than 3.5 to 4 mL of CSF is necessary. The most critical issue in a patient with suspected bacterial meningitis, however, is the initiation of antibiotics. The CSF examination and imaging studies can be deferred in this medical emergency.
During the course of treatment, most patients will undergo some cerebral imaging study. Computed tomographic (CT) scans are most useful in the initial presentation to exclude intracranial mass or bleeding, or to evaluate for other signs of increased intracranial pressure. However, magnetic resonance imaging (MRI) is most helpful for demonstrating any focal ischemia or infarction caused by the disease. When HSV meningitisis suspected, MRI should demonstrateenhancement of the temporal lobes. In tuberculous meningitis, enhancement of the basal region may be seen. An electroencephalogram (EEG) may be helpful in patients suspected of HSV meningitis. Within 2 to 15 days of the start of the illness, periodic sharp and slow wave complexes originating within the temporal lobes can be demonstrated at 2- to 3-second intervals. When the purpuric skin lesions are present, skin biopsy may demonstrateN meningitidisand can be helpful in the diagnosis. Age may give a clue regarding etiology of meningitis.
Therapy
Treatment of meningitis often is empiric until specific culture data are available. Because of the growing incidence of resistant pneumococci as well as meningococci, the recommended empiric therapy in most areas is a high-dose third-generation cephalosporin given concurrently with vancomycin. In other areas, if the disease presentation is typical for meningococcus (with the typical rash) or the organism is identified quickly on Gram stain of the CSF, therapy with high-dose penicillin can be started if the meningococcus in that area is known to be sensitive. Ampicillin is added when there is a suspicion of listeriosis. Acyclovir should be started for suspicion of HSVor four-drug antituberculosis (TB) therapy started if the presentation is suspicious for tuberculous meningitis. The administration of glucocorticoidsto reduce CNS (central nervous system) inflammation is controversial. One study in adults demonstrated decreased mortality in patients with S pneumoniaemeningitis who were given glucocorticoids. There is stronger data for steroids for H influenzae andS pneumoniaemeningitis in children. There is also some evidence for benefit of steroids in severe tuberculous meningitis.
Prevention of meningitis can be achieved through the administration of vaccines and chemoprophylaxisof close contacts. Specific vaccinations are available forH influenzaetype B and some strains ofS pneumoniaeand are now routinely administered to children.Meningococcal vaccinationis recommended for those living in dormitory situations, such as college students and military recruits, but not for the general population. Rifampin given twice daily for 2 daysor a single dose of ciprofloxacin is recommended for household and close contactsof an index case of meningococcemia or meningococcal meningitis.
