Current Diagnosis & Treatment in Infectious Diseases

Section II - Clinical Syndromes

7. Infections of the Central Nervous System

Zell A. McGee MD*

*The author is grateful to J. Richard Baringer, MD, Professor of Neurology, University of Utah School of Medicine, for his careful review of this chapter, his constructive suggestions, and the several sections he wrote on subjects that represent special areas of his expertise.

The signs and symptoms of infections of the central nervous system (CNS) are not specific to each type of infection (eg, brain abscess or meningitis), but certain clusters of signs and symptoms can limit the range of CNS infectious diseases that must be considered. The following elements of a patient's history, signs, and symptoms may indicate or accompany meningeal or parenchymal CNS infections, especially if one or more occur in the same patient: fever; headache; nausea and vomiting; confusion, obtundation, or uncharacteristic behavior; stiff neck; or focal neurologic dysfunction.

When these signs and symptoms follow those of infection of the upper or lower respiratory tract, the cluster suggests the transition of the respiratory tract infection to bacteremia or viremia and then its progression to meningitis or another type of CNS infection.


General Considerations

More than most other infectious diseases, acute bacterial meningitis threatens the life, personality, and functional ability of a patient. The disease may be obvious or quite subtle in its initial presentation. Empiric therapy usually relies on a one-step (or monosynaptic) thought process (disease ← antimicrobial agent) that is not optimal for managing most infectious diseases. Optimal recognition and management of acute bacterial meningitis use a progressive, three-step (or polysynaptic) thought process that is also effective for managing most other infectious diseases (Table 7-1).


The key findings in meningitis are the presence of fever, headache, stiff neck, nausea and vomiting, and, often, variable states of confusion. Note that neck stiffness, although usually present, is often overlooked. Although a stiff neck is not required to make the diagnosis of meningitis, its presence demands immediate pursuit of the diagnosis of meningitis.

Perhaps the most helpful indication that the diagnosis of meningitis should be considered seriously enough to warrant the performance of a spinal tap (if a thorough examination yields no signs of an intracranial mass or increased intracranial pressure) is the transition of a sore throat or other upper respiratory tract irritation to nausea and vomiting. Whereas most patients who actually have meningitis have fever and headache, the pattern of evolution of meningitis, especially meningococcal meningitis, is from sore throat to tachypnea (perhaps a sign of early meningococcemia with disseminated intravascular coagulation) and then to nausea and vomiting as the meningococcemia seeds the cerebrospinal fluid (CSF) space and establishes meningitis with cerebral edema.

The constellation of headache, fever, nausea, vomiting, or a combination of these symptoms should immediately prompt the consideration of meningitis, especially in the context of previous disease or irritation of the upper respiratory tract (eg, sinusitis, otitis media, or pharyngitis). Often patients with meningitis will complain of ocular pain or an increase in headache when turning their eyes from side to side. Although this sign is not specific for meningitis, its presence should prompt suspicion of the disease.

Although the accuracy of the clinical examination in the diagnosis of meningitis is limited by the paucity of prospective data, Attia et al (1999) have evaluated the clinical findings in meningitis and cite the 97% sensitivity and 60% specificity of the jolt test of Uchihara and Tsukagoshi (1991) in diagnosing meningitis. The jolt test, accentuation of headache by rapid movement of the head from side to side, appears to have potential usefulness, but more widespread systematic evaluation is needed before incorporation of the test into routine practice can be recommended.

Table 7-1. Polysynaptic thought process for managing infectious diseases.


Most Likely Organism

Best Antimicrobial1

eg, Meningitis


1. Patient's personal risk factors

2. Community risk factors (what's going around)

3. Physical examination

4. Laboratory: (Gram stain) cultures and imaging studies


1. Which antimicrobial is likely to be active against the most likely organism?

2. Which antimicrobial is delivered to the site of the infection?

3. Which antimicrobial has a bactericidal mode of action?

4. Which antimicrobial avoids the patient's special vulnerabilities (eg, allergy, myasthenia gravis, young age)?

1In known or suspected meningitis, the antimicrobial therapy should be initiated as soon as possible, ideally within 30 min after strongly suspecting or confirming the diagnosis.

In a febrile patient with a history of previous upper respiratory tract irritation, vomiting should elicit concern about meningitis rather than being considered a sign of gastroenteritis or “the flu.”

Note that almost all patients with bacterial meningitis give a history of upper respiratory tract irritation that can be interpreted as pharyngitis. However, health care personnel should consider the context of such complaints, and, if there is fever >101°F, nausea or vomiting, headache, confusion, or any signs of neurologic irritation, meningitis should be strongly suspected. The author has seen patients who suffered permanent neurologic damage because their meningitis was not recognized and health care personnel, using an algorithm for pharyngitis, gave oral antimicrobial therapy, which is inappropriate for meningitis.

Although patients often do not complain spontaneously of neck stiffness, they frequently will admit to the symptom if questioned. Detecting neck stiffness is best done by cupping the patients occiput in the examiner's hands, gently turning the head from side to side, which usually causes little discomfort, and then gently flexing the neck while observing the patient's face for signs of pain and feeling for sudden resistance as the neck is flexed. Modest degrees of meningeal irritation are usually evident with this procedure. Whereas the traditional Kernig and Brudzinski signs may be present in acute meningitis, in the author's experience they are present much less often than is neck stiffness and are less sensitive in the detection of minor degrees of meningeal irritation than is testing for neck stiffness as described above.

Once the diagnosis of meningitis has been seriously considered and care has been taken to assure that there are no signs of an intracranial mass (eg, no papilledema or focal neurologic abnormalities), a lumbar puncture should be performed.


Acute meningitis is most often caused by bacteria that have capsules (eg, Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae). These organisms are passed from person to person by droplet spread or mucosa-to-mucosa spread during close contact. Although some yeasts (eg,Cryptococcus neoformans) cause acute meningitis in patients with ostensibly normal immunity, they cause meningitis more often in patients whose cell-mediated immunity is compromised (eg, by lymphoma, AIDS, steroids, or other forms of iatrogenic immunosuppression), and yeast infections must be sought in such patients.

Empiric therapy entailing the choice of broad-spectrum antibiotics instead of organism-specific therapy is suboptimal for acute meningitis, because such therapy is at danger of being less active and less effective than therapy specifically targeted for the most likely organism. Therefore, optimal therapy entails predicting the most likely organism to be causing the meningitis and then administering the therapy that is optimal for that organism. Usually one can correctly deduce the most likely organism to be causing the meningitis by considering four kinds of information regarding the patient: (1) personal risk factors, (2) community risk factors, (3) physical examination, and (4) laboratory and imaging studies (see Tables 7-1,7-2,7-3 and 7-4).


Personal Risk Factors

The bacterial pathogen most likely to cause meningitis varies with the site of acquisition and the age of the patient (Table 7-2). Patients who are asplenic or alcoholic or who have preexisting ear or paranasal sinus infections are at greater risk of having infections with S pneumoniae..

Among patients who have conditions that allow access of stool to CSF, for instance, a pilonidal sinus or Strongyloides stercoralis infestation, Escherichia coli is often the most likely organism to be causing their meningitis.

In some cases, the most likely organism may be predicted by the nature of prior antimicrobial therapy. Certain broad-spectrum, oral antimicrobial agents such as ciprofloxacin or cefixime may predispose a patient to bacterial meningitis, apparently by eradicating normal nasopharyngeal flora and allowing overgrowth of meningitis-causing bacteria, especially S pneumoniae, which is less susceptible to these antibiotics than are normal flora. A substantial number of patients have developed fatal pneumococcal sepsis and meningitis while being treated with such antibiotics (Lee et al, 1991; Ottolini et al, 1991). Ironically, most of the antibiotics were prescribed for upper respiratory tract infections, bronchitis, and otitis media, which may not benefit from antimicrobial therapy (Gonzales et al, 1997; Nyquist et al, 1998).

Table 7-2. Value of locale of acquisition and age to predict the most likely organism to be causing the meningitis.1


Age Group

Most Likely Organism(s)

Community-acquired meningitis

<1 mo (neonatal)

Group B streptococci
Some S pneumoniae
L monocytogenes

1–23 mo (infants)

S pneumoniae
N meningitidis
Some group B streptococci
H influenzae

2–18 y

N meningitidis
S pneumoniae
Some H influenzae

19–59 y

S pneumoniae
N meningitidis
Some H influenzae

>60 y

S pneumoniae
Some L monocytogenes

Hospital-acquired or trauma-related meningitis

Any age

<10 d post-trauma: S pneumoniae, H influenzae (patient's flora)
>10 d post-trauma: K pneumoniae, P aeruginosa, E coli, other hospital flora

1Most of the data are from Schuchat et al. (N Engl J Med 1997;337:970), who did not include in their surveillance E coli or other enteric pathogens among infants <1 mo of age.

The microorganism causing the antecedent respiratory tract or other type of infection is the likely cause of meningitis in many patients. Patients with enteroviral meningitis have sometimes had recent contact with children or others with diarrhea. A recent episode of genital herpes should prompt consideration of a herpetic etiology of the meningitis.

Community Risk Factors

Cases of meningococcal disease may occur in epidemics or clusters, and state or local health departments may be helpful in predicting the most likely organism from such epidemiologic data.

Similarly, clusters of meningitis caused by Listeria monocytogenes have occurred in conjunction with the ingestion of raw and cooked meat, poultry, and, especially, unpasteurized dairy products such as cheese that have entered the commercial food supply contaminated with L monocytogenes.

Physical Examination

Several physical signs, considered in light of the patient's age, can be extremely helpful in correctly predicting the infecting organism (Table 7-3). If there are no physical signs suggesting the most likely organism, the organism can be predicted on the basis of the locale of acquisition of the meningitis and the patient's age as described above (see Table 7-2).

Laboratory/Imaging Studies

The laboratory findings in the CSF can also be helpful in either predicting or determining with certainty the most likely organism or type of organism to be causing the meningitis (Table 7-4).

Chest x-rays showing pneumonia in conjunction with meningitis suggest that the cause of the pneumonia may be the same as that of the meningitis; this association has been observed with N meningitidis and S pneumoniae infections. If the pneumonia in conjunction with meningitis is cavitary, organisms that cause cavitary pneumonia such as Staphylococcus aureus or Pseudomonas aeruginosa should be suspected.

Table 7-3. Value of physical examination in predicting the most likely organism to be causing meningitis.

Physical Sign

Most Likely Organism

Otitis media
Sacral pilonidal sinus
Petechiae (depends on age)

Purpura fulminans
Ecthyma gangrenosum

S pneumoniae
Stool flora, probably E coli
Young adults, N meningitidis
Children, H influenzae
N meningitidis
P aeruginosa > candida > other fungi, other gram-negative bacilli

Table 7-4. Value of CSF findings in predicting the most likely cause of meningitis.

Type of Meningitis

Leukocyte Cell Type



Other Tests

Bacterial meningitis


<50% of blood


PCR for some

Tuberculous meningitis


<50% of blood



Fungal meningitis



India ink3

Antigen 4

Viral meningitis



CSF culture
Stool culture

Carcinomatous meningitis

Lymphocytes, tumor cells

Very low

Cytologic exam

1PMN cells may be present early in disease.
2Limited availability of test.
3For cryptococci; relatively insensitive.
4For cryptococcus.
5For coccidioides.
6PMN cells may predominate in first 24 h.
7May be low in mumps.


It is important to initiate therapy as promptly as possible. In general, it is preferable to begin therapy after CSF and blood cultures have been obtained, but before the results of the laboratory examinations are available. Therefore, the hypothesis about the most likely organism should be used to initiate therapy, then the hypothesis should be tested by examining the CSF with nonspecific tests such as the leukocyte count and differential and CSF protein and glucose concentrations, all of which can be helpful in indicating groups of causative agents (see Table 7-4). A more sensitive and specific identification of the most likely organism often can then be obtained by performing a Gram stain on CSF subjected to cytospin slide centrifugation and culture and, if the Gram stain is negative, also testing the CSF for evidence of cryptococcal antigen and tuberculous infection, using polymerase chain reaction (PCR) or culture. Microscopic detection of the organism causing meningitis is more effective if the CSF is first subjected to cytospin slide centrifugation, which substantially increases the sensitivity of the Gram-staining endeavor (Shanholtzer et al, 1982). Rapid bacterial antigen tests were once used to attempt identification of the causative microorganism if prior antimicrobial therapy made it undetectable. However, bacterial antigen tests were found to be of “no detectable clinical benefit” in diagnostic and therapeutic decision-making (Perkins et al, 1995), and many laboratories no longer perform these tests.

If pneumococcal meningitis is likely (see Table 7-2), a premium should be put on culturing the organism from blood or CSF so that knowledge of its penicillin susceptibility can help facilitate design of an optimal treatment regimen. If specific tests such as PCR analysis of the CSF point to an organism different from the one originally hypothesized, the therapy can be changed to another specific therapy (such a change will seldom be necessary).

Whereas the foregoing considerations represent the optimal approach to acute bacterial meningitis, one must remember that tuberculous, cryptococcal, and occasionally coccidioidal meningitis also may have an acute onset and may produce clinical findings indistinguishable from those in acute bacterial meningitis.

Differential Diagnosis

Note that vomiting, although a common symptom of gastrointestinal disease, occurs frequently in meningitis. Meningitis is likely to be much more threatening to the life and function of the individual than is gastrointestinal disease, so one should not assume that vomiting in the febrile patient represents gastroenteritis.

A patient with meningococcal sepsis may have a normal or low total peripheral leukocyte count, but there is often an increased proportion of “bands” or immature polymorphonuclear leukocytes in the peripheral blood. In patients who have such laboratory findings in conjunction with other signs or symptoms of sepsis, strongly consider initiating parenteral therapy for sepsis, using antimicrobial agents appropriate for the most likely causative microorganism.

Syphilitic meningitis develops more often during the secondary or tertiary stages of the disease, generally at a slower pace than meningitis caused by other microorganisms, and presents with seizures in ~18% of patients with this disease. Thus, in patients with signs and symptoms suggestive of meningitis, especially seizures, syphilitic meningitis should be considered as part of the differential diagnosis, and appropriate serologic tests for syphilis should be performed on the serum and CSF.

Cautions Prior to Lumbar Puncture

It is very important to establish whether the patient with signs and symptoms of acute meningitis has papilledema, which is rare in acute meningitis without complications such as a mass lesion. A thorough examination should also be performed to detect any lateralizing findings (eg, hemiparesis or hemianopic field defect) or localizing findings (eg, aphasia), which might suggest the presence of some other process such as a brain abscess, subdural empyema, or cerebral infarction with mass effect. The presence of papilledema, localizing signs, or lateralizing signs mandates an imaging study before the performance of a lumbar puncture. A lumbar puncture performed in the presence of a mass lesion, particularly one that displaces intracranial structures, can result in a herniation syndrome and possibly death. However, antimicrobial therapy for the meningitis should be initiated before the patient is sent for the imaging study, as noted below.

In many emergency rooms, it is common practice to obtain a computed tomography (CT) scan for patients who have signs and symptoms suggestive of meningitis, before a diagnostic lumbar puncture is performed or antimicrobial therapy is instituted. Most authorities agree that any delay involved in obtaining such imaging studies could result in a significant hazard to the patient with meningitis if antibiotic treatment has not already been instituted. Bacteria multiply rapidly in the sheltered environment of the subarachnoid space, and the delays that are commonly encountered in obtaining imaging studies create a significant additional hazard to the patient. Therefore, if imaging studies are indicated (see previous paragraph), the patient should be stabilized, and optimal parenteral antibiotic therapy should be begun before such imaging studies are obtained. However, Baker et al (1994), after a systematic study of the efficacy of routine head CT scans prior to lumbar puncture in the emergency department concluded, “Routine use of CT scans in the absence of localizing signs prior to lumbar puncture in the emergency department is not indicated.”

In some instances it may be necessary to perform a lumbar puncture without CT or magnetic resonance imaging (MRI) to establish the diagnosis of meningitis in order to permit initiation of prompt, optimal, specific antibiotic treatment. For instance, if a patient with signs of meningitis (but with no suggestion of papilledema or lateralizing or focal neurological deficits) is cared for in a setting where imaging studies are not available, eg, a rural office or clinic, it may be necessary to perform a lumbar puncture to establish the diagnosis of meningitis and institute optimal parenteral therapy. In such a situation, if the patient is to be transferred to a tertiary facility, the parenteral antimicrobial therapy should be continued and part of the CSF, as well as blood cultures obtained before therapy, should be transported with the patient. In addition, in the midst of a community-wide epidemic of meningococcal meningitis or when the patient has signs of meningococcal sepsis (eg, petechiae or purpura fulminans) with meningitis, it is probably safe to do a lumbar puncture without antecedent CT or MRI imaging if there are no signs of an intracranial mass.

Once treatment of meningitis has commenced and the patient has been stabilized, it is the practice of some experts to image the brain at some time during the course of therapy because of the frequency of associated pathologic processes. These associated processes include paranasal or mastoid sinusitis, subdural empyemas or effusions, basilar skull fractures, intracerebral abscesses or infarctions, and hydrocephalus, many of which may require neurosurgical intervention. Other experts reserve CT or MRI scans for patients with signs of a mass lesion, patients who remain febrile for >5 days after initiation of optimal antimicrobial therapy, patients who have altered consciousness, or patients who were initially infected with bacteria such as S pneumoniae that are especially likely to cause sinusitis or loculated pus that requires drainage.

Optimally, for the diagnosis and therapy of most patients with known or suspected meningitis, the steps in Table 7-5 should be taken, but, if the presence of even questionable findings of papilledema, lateralizing signs, or localizing signs raises concerns over a possible mass lesion, or, if there is worsening headache or a diminishing level of consciousness, imaging studies should be considered as follows:

  1. Immediately Available CT Scan.If a CT scan can immediately be performed, obtain a CT scan and proceed to a lumbar puncture if no mass lesion is present, and follow the remainder of the steps in Table 7-5.
  2. CT Not Readily Available.If a CT scan is not readily available or a significant delay is anticipated, most experts recommend that blood cultures be obtained immediately and antibiotic treatment optimal for the most likely organism (see Tables 7-2 and 7-3) be instituted before the CT or other imaging study and before a lumbar puncture (see Treatment section below). The prior institution of antibiotic therapy will only minimally decrease the diagnostic sensitivity of CSF cultures and may still allow detection and identification of the causative microorganism by stains or PCR. The initial emergency therapy can be changed if findings of stains, cultures, or PCR on the CSF so indicate. A change in therapy will seldom be necessary. Especially in pneumococcal meningitis, with increasing resistance of pneumococci to beta-lactam antibiotics, it is helpful to culture the organism rather than simply detecting it with stains or PCR, because the viable organisms are necessary for determining the penicillin susceptibility of the infecting pneumococcus, which is information that may be important in designing an optimal antipneumococcal antimicrobial regimen.

Table 7-5. Management of the patient with obvious meningitis.

If the patient has obvious meningitis (fever, stiff neck, and confusion or coma), set an ideal goal of allowing yourself 30 min to have an IV infusing the best antibiotic for the most likely organism to be causing the meningitis.
Suggested Use of the 30 Min
10 min to confirm the diagnosis and get history (eg, drug allergy, previous meningitis, recent sinusitis or trauma) and assure that there is no papilledema and that there are no focal neurological deficits that might suggest a mass lesion (such findings indicate that a spinal tap may result in a herniation syndrome)
5 min to start an IV and draw blood cultures
10 min to do a spinal tap (if no signs of a mass lesion are present)
Do not examine the CSF yet.
5 min to start an intravenous antibiotic appropriate for the most likely organism as judged by the patient's age and other risk factors (see Tables 7-2, 7-3 and 7-4 and 7-6).
Now Examine the Spinal Fluid
Change antibiotics if necessary; it rarely will be necessary if guidelines for predicting the most likely organism (see Tables 7-2 and 7-3) are followed in conjunction with picking the best antimicrobial agent for the most likely organism (see Table 7-6).

Patients with known or suspected meningitis should not be sent out on oral antibiotics, but should be admitted to the hospital and treated with parenteral antimicrobial agents that are optimal for the most likely organism.


To put the imperative for speed in initiating therapy into more concrete terms, some experts have suggested a goal of allowing no more than 30 min from the time of clinical diagnosis to starting an IV infusion of the best antibiotic for the most likely organism to be causing the meningitis. A suggested use of the 30 min appears in Table 7-5 and assumes that the above-mentioned precautions and procedures regarding signs of a mass lesion will be observed.

Intravenous antimicrobial agents are the optimal types of therapy for acute bacterial meningitis. Specific, optimal antimicrobial agents for the therapy of acute meningitis that is known or suspected to be caused by particular organisms are reviewed in Table 7-6. The antimicrobial agent chosen should meet a number of criteria, which are listed under “Best Antimicrobial” in Table 7-1. As noted, the antimicrobial agent chosen should avoid the patient's special vulnerabilities. For example, if possible, the patient should not be given an antibiotic to which he or she is allergic; patients with myasthenia gravis, which causes intrinsic neuromuscular blockade, should not be given aminoglycosides, which may induce further neuromuscular blockade; and, if possible, patients with hemolytic anemias such as sickle cell disease should not be given chloramphenicol, which diminishes erythrocyte production.


It may be difficult to separate the complications of the bacteremia and septicemia that are associated with the meningitis from the complications of the meningitis per se. The complications of the septicemia include coagulation disorders such as disseminated intravascular coagulation (manifested in meningococcemia as a petechial rash and “purpura fulminans” or in some cases as hemorrhagic adrenal necrosis—“Waterhouse-Friderichsen syndrome”), myocarditis with congestive heart failure, shock, and prolonged fever. The more frequent complications of the meningitis per se result from the inflammatory reaction, including tumor necrosis factor-alpha (TNF-α) induction, which may cause damage to cranial nerves with resulting ophthalmoplegias, deafness, and blindness. Seizures or hydrocephalus may occur as early or late complications. In meningitis caused by H influenzae in children, some of these complications appear to occur less frequently if dexamethasone is administered in conjunction with antimicrobial agents to diminish the production of TNF-α (see Table 7-6). No comparable information is available for meningitis in adults or for meningitis caused by other bacteria.


Although the mortality rate for bacterial meningitis varies with the specific etiologic agent and the clinical circumstances, especially the age of the host, with early diagnosis and prompt, targeted (not broad-spectrum) antimicrobial therapy, the mortality rates for meningococcal and H influenzae meningitis are generally < 10% and 5%, respectively. Pneumococcal meningitis has a worse prognosis, with mortality rates of ~20%; in addition, neurologic complications, such as hydrocephalus, subdural empyema, seizures, and cranial nerve palsies, occur more frequently in meningitis caused by S pneumoniae.

Prevention &Control

A first line of defense against meningitis is the induction of anticapsular antibodies by means of vaccines or natural exposure. Timely administration of H influenzae type b (Hib) conjugate vaccine has dramatically reduced the frequency of H influenzae meningitis in the United States; however, in some states, less than half of the eligible children have been immunized.

Table 7-6. Best antimicrobial regimens for specific most likely organisms.



N meningitidis

· Adults: Penicillin G,3 4 million U by volutrol over 30 min every 4 h

· Children older than 28 d: Penicillin G,3 50,000 U/kg IV every 6 h

· Children 7 d or younger: Penicillin G,3 50,000 U/kg IV every 12 h

· Penicillin-allergic patients: Chloramphenicol

· Some experts add dexamethasone (as described below for Hib)
Penicillin may cure the meningitis but fail to eradicate the nasal carrier state of the patient. To prevent postdischarge transmission of meningococci from the patient to siblings or other contacts, eradicate the carrier state of the patient with rifampin before discharge.4 For children older than 1 m of age, give rifampin, 10 mg/kg (maximum dose, 600 mg) PO every 12 h for a total of 4 doses in 2 d. For children ≤ 28 d old, the dosage is 5 mg/kg PO every 12 h for a total of 4 doses in 2 d. For teenagers or adults, the dosage is 600 mg PO every 12 h for a total of 4 doses in 2 d.

Group B streptococci

· Adults: ampicillin, 2.0 g IV every 4h + cefotaxime, 2.0 g IV every 6 h

· Neonates: ampicillin, 50 mg/kg IV every 12 h + cefotaxime, 50 mg/kg IV every 12 h
With either regimen, repeat CSF exam/culture 24–36 h after start of therapy.

S pneumoniae (pneumococcus)

· Adults and children older than 1 m: If the pneumococcus is known to be susceptible to penicillin (MIC ≤ 0.1 µg/ml), use penicillin as above; otherwise, begin therapy with vancomycin, 15 mg/kg IV every 6 h
PLUS either5:
Cefotaxime, 50–75 mg/kg IV every 6 h
(8–28 d > old)
Ceftriaxone, 100 mg/kg IV at diagnosis, 12 h, then per day thereafter
(>28 d old)
(Adults) ceftriaxone, 2 g IV every 12 h
Adjust the regimen when the susceptibility of the pneumococcus has been quantitated (eg, if the patient is responding well and the pneumococcus is susceptible to the cephalosporin, discontinue vancomycin).
Some experts add dexamethasone (as described below for Hib).


There are three major components of therapy:

1. Antibiotics:

o   Adults: Cefotaxime, 2 g IV every 4–6 h

o   Children >28 d old: Ceftriaxone, 100 mg/kg IV per day

o   (8–28 days old) Cefotaxime, 50 mg/kg IV every 8 h6

Ampicillin can be used for therapy of Hib meningitis only if the infecting strain is demostrated not to produce β-lactamase

2. Inhibition of TNF-α production:
Data from studies in children with H influenzae meningitis indicate that an inhibitor of TNF-αproduction, dexamethasone, 0.4 mg/kg IV every 12 h for 2 d of antibiotic therapy, reduces the neurologic sequelae of meningitis (Lebel et al, 1988). There are no completely comparable data in adults or in meningitis caused by other pathogens, but, if there were no possible contraindication, such as a history of TB, many experts woiuld use dexamethasone in meningococcal, pneumococcal, and other bacterial meningitides in which the inflammatory reaction seems to be more deleterious than helpful to the patient.

3. Eradicate carrier state of treated patients with rifampin prior to discharge4:

For children older than 1 mo, give rifampin, 20 mg/kg (maximum dose, 600 mg) PO daily × 4 d. For adults or teenagers, each dose is 600 mg. Some experts forego this therapy if the patient was treated with cefotaxime or ceftriaxone, either of which eradicates nasal carriage of Hib.

L monocytogenes

· Adults: Ampicillin, 2 g IV every 4 h (some experts add gentamicin, 2 mg/kg loading does, than 1.7 mg/kg every 8 h)7

· Children >28 d old: Amplicillin, 50 mg/kg per 6 h + gentamicin, 2.5 mg/kg IV per 8 h

· Neonates: Ampicillin, 50 mg/kg IV per 12 h + gentamicin, 2.5 mg/kg IV per 18–24 h

S aureus

· Adults: Nafcillin or oxacillin (2 g IV every 4 h)
Vancomycin (1.0 g IV every 6–12 h) plus rifampin, 600 mg PO per day

· Children >28 d old: nafcillin or oxacillin (37 mg/kg IV per 6 h) or vancomycin (40–60 mg/kg IV divided every 6 h).

· Neonates: Nafcillin or oxacillin (25 mg/kg IV per 12 h).

Gram-negative bacilli

(not H influenzae)

Klebsiella spp., E coli, etc

· Adults: Ceftazidime, 2.0 g IV every 8 h,
PLUS gentamicin, 2 mg/kg IV loading dose, 1.7 mg/kg every 8 h thereafter

· Children: Seek pediatric infectious disease consultation

Pseudomonas, Enterobacter, and Acinetobacter species

Often develop resistance to cephalosporins during therapy; therefore, susceptibility testing should be done on each successive isolate,8 and if cephalosporin resistance arises, some experts treat older children, teenagers, and adults with systemic plus intraventricular aminoglycosides, as follows (an infectious disease consultation is recommended):
Give intraventricular gentamicin, 0.03 mg/ml of CSF volume (the total volume of the CSF can be estimated with reasonable accuracy by the neuroradiologist)
Intraventricular amikacin, 0.1 mg/ml CSF volume
Standard intravenous therapy with the same aminoglycoside

1Most of these therapeutic recommendations are from The Sanford Guide to Antimicrobial Therapy 2000 (Gilbert et al. 2000), the American Academy of Pediatrics Red Book, or both. For therapy of children whose age or weight does not conform to the guidelines here, the reader is advised to refer to The Sanford Guide to Antimicribial Therapy 2000 [Tables 1 (3)-1 (5) and 16] and the pediatric Red Book.
2Use half normal saline or saline for IV diluent fluid; D5/water administration may result in cerebral edema or hyponatremic seizures if inappropriate antidiuretic hormone secretion accompanies the meningitis, as is often the case.
3Avoid bolus injection of penicillin, which may precipitate seizures or cause respiratory arrest.
4Chemoprophylaxis regimens to protect individuals exposed to an index patient with invasive disease cause by N meningitidis or Hib or to eradicate the carrier state in a treated patient are shown in boldface.
5Recent studies in children suggest that meropenem, 1 g IV every 8 h, can substitute for the vancomycin/cephalosporin regimen (see Odio et al, 1999). Many experts add dexamethasone to the antimicrobial regimen to decrease TNF-α production and help prevent nerve damage that may result in blindness, deafness, or both.
6A recent, prospective, randomized, multicenter trial showed meropenem to equal cefotaximein efficacy and safety in meningitis of children (Odio et al, 1999). Further, in that study both drugs were administered without vancomycin. The S pneumoniae isolates with decreased susceptibility to penicillin or cefotaxime were susceptible to meropenem.
7Others prefer to treat adults with sulfamethoxazole-trimethoprim, 15–20 mg/kg, trimethoprime quivalent, in equally divided doses given every 6–8 h. Sulfamethoxazole-trimethoprim is contraindicated in infants <2 mo of age.
8Some clinical microbiology laboratories save the first isolate from an infected site, and when the same microorganism is subsequently isolated from that site, report the first set of susceptibility data. This pratice may result in failure to detect the transition of an initially cephalosporin-susceptible isolate to a cephalosporin-resistant isolate during cephalosporin therapy. Thus, susceptibility testing should be done on each successive isolate in meningitis caused by Pseudomonas, Enterobacter, or Acinetobacter spp., if the patient is treated with a cephalosporin.

By reducing pneumococcal bacteremia, a pneumococcal vaccine theoretically should decrease the frequency of pneumococcal meningitis, and the limited immunogenicity of some of the pneumococcal serotype polysaccharides in children < 2 years old has recently been circumvented by conjugating the polysaccharides to a diphtheria protein. The resulting, currently available, 7-valent pneumococcal vaccine has been shown to prevent pneumococcal carriage and invasive pneumococcal infections, including meningitis, in children < 2 years old.

A 23-valent pneumococcal vaccine is recommended for all patients aged ≥65 and for nursing home residents, as well as for immunocompromised and other high-risk patients. Anatomic or functional asplenia is an absolute indication for the vaccine, and the vaccine should be given, if possible, at least 2 weeks before splenectomy. The vaccine is also recommended 2 weeks before beginning any immunosuppressive treatment.

The conjugate pneumococcal vaccine is indicated for the active immunization of infants and toddlers against invasive disease caused by pneumococci of the capsular types represented in the vaccine. The routine schedule is vaccination at 2, 4, 6, and 12–15 months of age. This vaccine is not for use in adults.

A quadrivalent meningococcal vaccine (including groups A, C, Y, and W135) is available. If there is an epidemic or cluster of cases in a closed population, such as that of a college campus or group home, or for individuals traveling to countries where meningococcal disease is epidemic, the use of the meningococcal vaccine should be considered. The quadrivalent vaccine is recommended for use in epidemics of meningococcal disease caused by strains of any group whose capsular type is represented in the vaccine. Help in determining the need for a vaccine administration program and in planning such a program should be sought from the appropriate state health department or from the Centers for Disease Control [telephone (404) 639-2215].

Protection of Contacts in Cases of Meningitis

  1. Meningococcal Meningitis.Individuals who have had prolonged close contact with a meningococcal meningitis patient, especially those who have had mucosa-to-mucosa contact with such a patient, are at risk of becoming newly colonized with meningococci either from the patient or from the same source as the patient. It is newly colonized individuals, lacking serum anti-meningococcal antibodies, that are at greatest risk of developing meningococcemia or meningitis. The purpose of chemoprophylaxis is to eradicate the newly acquired meningococci and their progeny before they cross the nasopharyngeal epithelium and enter the bloodstream.

The physician managing a patient with meningococcal meningitis should notify local public health authorities about the case and work out a strategy for announcing promptly and proactively who does need and who does not need chemoprophylaxis.


Meningococcal vaccine should not be used instead of rifampin chemoprophylaxis for individuals at risk, because the response to meningococcal vaccine is not rapid enough to meet the immediate need of protecting the contacts of patients with meningococcal meningitis. Such at-risk individuals should be given chemoprophylaxis with rifampin.

Chemoprophylaxis should be given to close contacts of the patient (eg, family members, girlfriends or boyfriends, or others who may have had direct contact with the index patient's oral secretions). Chemoprophylaxis is not recommended for casual contacts, such as individuals with no history of direct exposure to the index patient's oral secretions (eg, school- or workmates). Those medical personnel who have had mucosa-to-mucosa contact with victims of meningococcal disease (eg, through mouth-to-mouth resuscitation, intubation, or suctioning before antibiotic therapy is begun) appear to be at risk and should receive chemoprophylaxis. Other medical personnel appear to be at minimal risk, but most experts would offer them chemoprophylaxis if they were exposed to a case.

The chemoprophylaxis regimens for protecting individuals exposed to a case of invasive disease caused by N meningitidis or Hib are the same as those used to eradicate the carrier state of the index patient prior to discharge from the hospital (see boldfaced text under the respective organisms in Table 7-6). The rifampin powder in the proper dosage can be made into a liquid formulation or incorporated into other vehicles such as applesauce for young children.

  1. H influenzaeMeningitis.

The recommendation for chemoprophylaxis for contacts of cases of Hib meningitis is as follows: “In those households with at least one contact younger than 48 months whose immunization status against Hib is incomplete, rifampin prophylaxis is recommended for all household contacts, irrespective of age” (1997 Red Book, p. 223). See Table 7-6 for the recommended rifampin prophylaxis for protection of individuals exposed to a case of invasive Hib disease.

Because penicillins and some cephalosporins—antimicrobial agents often used to treat meningococcal or H influenzae meningitis—do not penetrate human cells well, meningococci and H influenzae organisms may remain safely inside cells of the nasopharyngeal mucosa of a patient cured of meningitis and emerge later to cause meningitis in the patient's siblings. Therefore, depending on the type of therapy of a patient with meningitis, the patient may need to be given chemoprophylaxis-like antimicrobial therapy to eradicate his or her carrier state before discharge. Such predischarge therapy is recommended for patients with either meningococcal or H influenzae meningitis and, for children older than 1 month, should consist of rifampin given essentially as indicated for chemoprophylaxis of contacts and detailed in Table 7-6. Some experts do not give such therapy if the cephalosporin used for treatment of the meningitis was cefotaxime or ceftriaxone, either of which appears to eradicate nasopharyngeal foci.


Essentials of Diagnosis

  • Signs and symptoms suggestive of the aseptic meningitis syndrome include fever, headache, nausea, and vomiting.
  • CSF pleocytosis is present.
  • Gram's stains as well as routine bacterial and fungal cultures are negative.

Some patients who present with the signs and symptoms of meningitis have CSF pleocytosis, but they also have negative Gram stains and routine bacterial cultures of the CSF, and they have no other evidence (such as positive blood cultures) to indicate the etiology of the meningeal inflammation. In considering the management of such patients, it is helpful to designate them as having the aseptic meningitis syndrome rather than “viral meningitis” because some of these patients have proven to have infectious processes that require antimicrobial therapy (Table 7-7), which is not indicated for most cases of viral meningitis.

Diagnosis and management of the aseptic meningitis syndrome and optimal care of the patient is made more difficult if a patient with the aseptic meningitis syndrome is casually diagnosed as having viral meningitis, with a resulting cessation of attempts to make an etiologic diagnosis or to determine the cause of the meningeal inflammation.

Table 7-7. Some antimicrobial-requiring causes of the aseptic meningitis syndrome.1

Amebic meningitis
Brain abscess
Contiguous sinusitis, otitis
Epidural abscess
Fungal meningitis
HIV meningitis
HSV2 aseptic meningitis
Infectious endocarditis
Lyme disease
Mollaret's meningitis1
Syphilitic meningitis
Tuberculous meningitis
Vertebral osteomyelitis (occasionally)

1Although herpes simplex virus has been associated with some cases of Mollaret's meningitis (Tang et al, 2000), there are insufficient data to warrant recommendations for antiviral therapy at this time.


General Considerations

Although viral infection is the most frequent cause of aseptic meningitis syndrome, there are many antimicrobial-requiring causes of the syndrome (see Table 7-7). Arthropod-borne viruses (arboviruses) cause disease more often in late summer and early fall; enterovirus disease follows a similar seasonal pattern, with echoviruses and coxsackieviruses predominating. Mumps virus meningitis occurs more often in late winter and early spring. Meningitis due to herpes simplex virus may occur at any time, often in association with a first episode of genital herpes infection.

Clinical Findings

In general, patients with aseptic meningitis syndrome are alert and complain of severe headache, primarily when they turn their eyes to one side or the other or flex their necks. They often seek a dark, quiet room. They rarely become confused or obtunded; so, if confusion or obtundation is evident, bacterial meningitis becomes much more likely. Nevertheless, patients in the early stages of bacterial meningitis can look exactly like those with the aseptic meningitis syndrome.

To determine the cause of the aseptic meningitis syndrome in a particular patient, it is helpful to consider three characteristics of the patient's illness: (1) the pace of development of the illness, (2) the presence or absence of focal or lateralizing neurologic findings, and (3) the presence or absence of confusion.

  1. The Pace of Development of the Illness—Depending on the underlying disease and the specific causative microorganism, the development of signs and symptoms of meningeal inflammation may be relatively slow (taking weeks to months) or rather rapid (taking hours to days). Tuberculous and fungal meningitis, as well as syphilitic meningitis and meningeal inflammation caused by bacterial endocarditis, generally develop at a slower pace, whereas pyogenic bacterial meningitis and viral meningitis develop more rapidly (over hours to days). Tuberculous meningitis and fungal meningitis are most expeditiously diagnosed if consultation with a microbiology laboratory is sought, so that optimal media and genetic probing techniques can be used to test the CSF. Similarly, the most incisive serologic tests for syphilis should be used in consultation with an immunology laboratory if syphilis appears to be a likely etiologic agent. Syphilitic meningitis develops more often during the secondary or tertiary stages of the disease and presents with seizures in ~18% of patients. Thus, in patients with signs and symptoms suggestive of meningitis, especially seizures, syphilitic meningitis should be considered as part of the differential diagnosis, and appropriate serologic tests for syphilis should be performed on the serum and CSF.
  2. The Presence or Absence of Focal or Lateralizing Neurologic and Other Findings—Whereas acute bacterial meningitis may cause cranial nerve abnormalities such as deafness or ophthalmoplegias, viral meningitis seldom causes such neurologic dysfunction. Similarly, brain abscesses, even if they have not ruptured into the subarachnoid space, may cause CSF pleocytosis in the absence of detectable bacteria in the CSF. Brain abscesses are more likely than bacterial or viral meningitis to cause focal neurological findings such as hemiparesis or aphasia. Spinal epidural abscesses, which may cause fever, CSF pleocytosis, and focal neurologic deficits, are usually accompanied by pain and percussion tenderness over the spine. With both brain abscesses and spinal epidural abscesses, CT scans with enhancement or MRI scans may be required to determine the cause of the culture-negative meningeal inflammation.
  3. The Presence or Absence of Confusion—In general, patients with aseptic meningitis syndrome as a result of viral meningitis are alert; therefore, if confusion or obtundation is evident, a bacterial etiology or some other nonviral etiology of the meningeal inflammation is more likely.
  4. Signs and Symptoms.Signs and symptoms suggestive of the aseptic meningitis syndrome depend on its underlying etiology, but often include fever, headache, nausea, vomiting, and neck stiffness.
  5. Laboratory Findings.CSF pleocytosis is present. Gram stain and routine cultures are negative. The CSF glucose, protein, leukocyte count, and differential can be helpful in determining the cause of the syndrome (see Table 7-4).
  6. Imaging.A number of the antimicrobial-requiring causes of aseptic meningitis syndrome require imaging studies to identify the lesion for diagnosis, optimal antimicrobial therapy, and, if indicated, surgical drainage. Whereas the CSF in true viral aseptic meningitis has a lymphocytic pleocytosis, abscesslike processes, including contiguous sinusitis, often have predominantly polymorphonuclear leukocyte pleocytosis of the CSF. Thus, the presence of the aseptic meningitis syndrome plus clinical signs suggesting the presence of a mass lesion, especially if there is polymorphonuclear pleocytosis of the CSF, should prompt imaging studies of the areas likely to be involved. A CT scan may suffice if acute intracranial hemorrhage is a possibility or if the patient cannot remain motionless in an MRI scanner; otherwise, MRI scans are the preferred imaging modality. Brain abscesses may not be visualized on CT scans unless contrast enhancement is used (Figure 7-1). Thus, contrast enhancement should be used with CT scans that are performed because a brain abscess is in the differential diagnosis. If a brain abscess is a possibility, a CT scan should not be considered to be completed unless it was done with contrast enhancement.

Figure 7-1. Effect of the use of contrast enhancement with CT scans on detection of brain abscesses. Two CT scan images made in the same plane within the head, ~30 min apart. (a) CT scan without contrast enhancement; (b) CT scan at the same level but with contrast enhancement, showing six areas of brain abscess or cerebritis not demonstrated in a. Reprinted by permission from the Southern Medical Journal 75:1261, 1982.


Differential Diagnosis

There are a substantial number of causes of aseptic meningitis syndrome, which can be life-threatening if not treated appropriately, sometimes with antimicrobial agents (see Table 7-7). The antimicrobial-requiring causes of aseptic meningitis syndrome should be excluded before embarking on an extensive workup of the non-antimicrobial-requiring causes (Table 7-8).

Some antibiotics and other pharmaceutical products can induce aseptic meningitis syndrome (Table 7-9). Whereas infectious causes of the meningitis should be excluded first, the drugs that cause meningitis are usually not critical, and substitutions of drugs that do not cause meningitis can easily be made. In a patient with meningitis who is having seizures, treatment with phenytoin usually suffices when intravenous administration is necessary; carbamazepine may be used when oral administration is possible, keeping in mind that it rarely may produce an aseptic meningitis syndrome.

To avoid inducing drug-related meningitis, avoid antimicrobial treatment of respiratory tract infections (eg, sinusitis and pneumonia) with oral antibiotics that do not have optimal activity against pneumococci and other streptococci. A substantial number of patients have acquired fatal pneumococcal sepsis and meningitis while taking such antibiotics. For instance, life-threatening pneumococcal and other streptococcal infections, including meningitis, have complicated therapy with the following oral antimicrobial agents: ciprofloxacin (Lee et al, 1991; Righter, 1990) and cefixime (Ottolini et al, 1991).

Table 7-8. Some non-antimicrobial-requiring causes of the aseptic meningitis syndrome.

Chemical meningitis
Cyst-related meningitis
Drug-induced meningitis (eg, ibuprofen, sulfa-trimethoprim)
Leptospiral meningitis
Mollaret's, lupus-, sarcoid-, and Behçet-associated meningitis
Neoplastic meningitis
Viral meningitis (most)

Table 7-9. Pharmaceutical products that may cause meningitis.






Joffeet al, 1989


Asperilla & Smego, 1989


OKT-3 monoclonal antibody2

CDC, 1986; Martin et al, 1988



Simon et al, 1990

Nonsteroidal anti-inflammatory drugs

Ibuprofen Naproxen

Jensenet al, 1987
Sylvia etal, 1988


Ruppert & Barth 1981


Ballas & Danta 1982

1Beware in AIDS patients receiving trimethoprim-sulfamethoxazole prophylaxis—this meningitis might be mistaken for cryptococcal or other meningitis.
2Might be mistaken for cryptococcal meningitis.


The complications of aseptic meningitis syndrome depend on its etiology. If caused by a pharmaceutical product such as ibuprofen, cessation of the inciting drug usually results in disappearance of the meningitis without complications. On the other hand, aseptic meningitis syndrome resulting from a brain abscess may be fatal if the brain abscess is not identified and treated properly, so that it is allowed to rupture into the CSF space.


As with bacterial meningitis, the antimicrobial therapy should be specifically targeted toward the most likely organism to cause the aseptic meningitis syndrome. For instance, the most likely organism to cause an epidural abscess is S aureus, whereas multiple brain abscesses associated with endocarditis are likely to be caused by the same organism that is infecting the heart valves.


In some patients, the best therapy for aseptic meningitis syndrome may be stopping a drug that is causing the meningitis. For instance, in a patient with AIDS who develops aseptic meningitis syndrome while receiving sulfa-trimethoprim prophylaxis against Pneumocystis carinii infections, it would be reasonable, after excluding infectious causes of the aseptic meningitis syndrome, to change the prophylaxis from sulfa-trimethoprim, which can cause an aseptic meningitis syndrome (see Table 7-9), to pentamidine for Pneumocystis prophylaxis. Antiviral therapy is not indicated for most cases of viral meningitis.


The prognosis of aseptic meningitis syndrome is the same as that of its underlying cause. For instance, neoplastic meningitis as the cause of aseptic meningitis syndrome has a dire prognosis, whereas drug-induced aseptic meningitis syndrome and virus-caused aseptic meningitis syndrome have an excellent prognosis.

Prevention & Control

Aseptic meningitis syndrome has such diverse causes that there is no single means of prevention and control. For instance, syphilis-related aseptic meningitis syndrome might be prevented by the use of condoms, and Lyme disease-related aseptic meningitis syndrome might be prevented by using an insect repellent that protects against the Ixodes tick vector.


Essentials of Diagnosis

  • If caused by infection, the progression of dementia is over weeks to months rather than years.
  • Frontal lobe abscesses may produce dementia without lateralizing or localizing signs.
  • Creutzfeldt-Jakob disease should be considered in middle-aged patients with dementia that progresses over a few weeks.

Most dementing processes with infectious causes progress subacutely, that is, over weeks to months rather than over a course of years. A more slowly progressive course may be seen occasionally with communicating hydrocephalus, as a result of prior meningeal infection and interference with reabsorption of CSF. The dementia of tertiary syphilis may also progress over a very long time course.

Frontal Lobe Infections

Infections localized to the frontal lobes of the brain can present as dementias with few other manifestations. For example, a brain abscess in the frontal lobes may fail to produce lateralizing or localizing signs that would be obvious if the abscess were located elsewhere in the brain. Progressive multifocal leukoencephalopathy (PML) (see Chapter 45), even though a disease predominantly affecting the white matter can be present in the frontal lobes and produce dementia prior to the appearance of focal deficits. Although previously encountered as a rare complication of lymphoma or Hodgkin's disease, PML is now most often seen as a complication of AIDS. Dementia in AIDS is commonly seen in the late stages of the process, where it appears to be a direct result of the viral infection. The dementia is characterized by slowness of thought, apathy, and inability to perform consecutive tasks. Loss of motor functions with ataxia and spasticity are seen as the disease progresses. Dementia becomes increasingly frequent as AIDS progresses, with 50–75% of patients affected in the terminal course of the disease.

Creutzfeldt-Jakob Disease

In middle-aged patients with dementia progressing over a few weeks, one must consider the possibility of Creutzfeldt-Jakob disease, which appears to be a prion disease (Ferrer et al, 2000). The dementia in these patients often presents abruptly and worsens perceptibly every few days to weekly, evolving into a state of mutism within 2–5 months. Myoclonic jerking of limb and trunk muscles often accompanies the process, and the patients often startle easily. The electroencephalogram is always abnormal and sometimes may show a characteristic periodic burst-suppression pattern. The CSF is usually normal. An unusual protein has recently been described in the CSF of Creutzfeldt-Jakob patients, but its presence is not sufficiently specific to serve as a diagnostic test. Recently a few cases of Creutzfeldt-Jakob disease have been described in which MRI has demonstrated increased signal in the anterior striatum.

Although Creutzfeldt-Jakob disease, as it is seen sporadically, is not due to an infection, it is thought to result from a mutation in the prion protein gene with production of abnormal isoforms of normal prion proteins; these abnormal prion proteins, if transmitted into another human host, are infectious and, after prolonged incubation, cause the same disease in the recipient. Examples have been the occurrence of the disease in recipients of corneal transplants, dura mater grafts, and human-derived pituitary growth hormone after incubation periods of many months to many years. A variant form of the disease has recently appeared in Great Britain in young individuals, perhaps related to ingestion of beef from animals afflicted by “mad cow disease,” another disorder related to infectious prions.



Essentials of Diagnosis

  • History: known or recently acquired valvular heart disease plusprior infectious processes (eg, staphylococcal sepsis), genitourinary or dental procedures, or intravenous drug use; presence of indwelling intravenous catheters; immunocompromised host predisposed to fungal infections.
  • Antecedent signs of infection: fever and chills, heart murmurs.
  • Signs of systemic embolism: ocular (Roth spots and other hemorrhages); skin or mucosal (petechiae, Osler's nodes); renal (hematuria); splenic (abdominal pain).
  • Laboratory studies: imaging of brain, CSF analysis, cardiac echo studies, blood cultures.

Infections as a cause of stroke are uncommon but must be considered in young individuals, in patients with valvular or congenital cardiac disease, or in immunocompromised hosts. Stroke in young individuals is less often due to atherosclerosis or hypertension and more often related to thrombosis or endocarditis complicating congenital or acquired valvular heart disease as a result of intravenous drug use, right-to-left cardiac shunts, or combinations of the above.

Bacterial Endocarditis

Bacterial endocarditis must always be considered in at-risk individuals, particularly if there is intravenous drug use or if the patients have recently undergone oral or genitourinary surgery or have a prosthetic cardiac valve (see Chapter 11). Embolic infarctions of brain in these individuals, although dominantly in the middle cerebral distribution, can occur in any vascular distribution and are often multiple, frequently in the distal territories of the cerebral vessels, and most frequently encountered when the causative organism is S aureus. The formation of mycotic aneurysms at the site of embolism is not uncommon, and may occur late in the course of the condition. Rupture of the mycotic aneurysm with subarachnoid hemorrhage is uncommon, but, when it occurs, is frequently fatal. The management of these problems, if caused by infective endocarditis, requires prolonged intravenous optimal antibiotic therapy and often repair or replacement of damaged cardiac valves.

Clues to the presence of subacute bacterial endocarditis include known previous congenital or rheumatic heart disease or rheumatic fever and the development of anorexia, backaches, myalgia, or signs of emboli in the spleen, kidney, eyes, or skin. The foregoing signs may all be easily overlooked if attention is devoted exclusively to the neurological phenomena. Repeated blood cultures may be required to identify the causative organism; identification and determination of the organism's susceptibility to antibiotics is of critical importance in determining the nature and duration of treatment with intravenous antibiotics.

Fungal Infections

Immunocompromised hosts, particularly if neutropenic or diabetic, are susceptible to fungal diseases and, of these, Candida, Aspergillus, and Mucor species have a predilection for invading the walls of cerebral blood vessels, resulting in stroke syndromes. The source for Aspergillus infection of cerebral vessels is often in the respiratory tract (see Chapter 75). Candida infection with involvement of cerebral vessels is seen in association with prolonged use of intravenous lines and in intravenous drug users (see Chapter 73). Mucor infections are characteristically seen in diabetic patients with frequent episodes of acidosis (see Chapter 75). Branches of the internal carotid artery, cranial nerves III through VI, and orbital tissues are often involved.

Other Meningeal Infections

Stroke syndromes may be seen in a variety of meningeal infections as a result of the involvement in the inflammatory exudate of penetrating vessels at the base of the brain. Often such vascular involvement is seen relatively late in the course of a meningeal infection and is related perhaps to the duration and intensity of the inflammatory process. It is also seen in acute bacterial meningitides caused by pneumococci (see Chapter 47) or H influenzae (see Chapter 56), in subacute meningitides caused by tuberculosis or fungal infections, and in low-grade chronic meningeal infections such as those caused by syphilis (see Chapter 64). It is rarely observed in viral meningitides but can be seen in the aftermath of herpes zoster (see Chapter 33) when it affects the trigeminal nerves, presumably resulting from a zoster infection of adjacent cranial vessels.


Essentials of Diagnosis

  • Antecedent fever or peripheral bacterial infection.
  • Development of back pain and tenderness, often with radicular pain.
  • Development of paraparesis with involvement of the bladder.


Infections, along with tumors, can cause acutely or subacutely developing spinal cord deficits, frequently in the form of a paraparesis with lower-extremity weakness, paralysis of bladder function, and sensory deficits below a segmental spinal level.

Epidural Abscess

Epidural abscess is the most urgent infectious process causing a cord deficit. This infection usually originates in lung, skin, or elsewhere and spreads hematogenously to the epidural space, where the abscess typically causes radicular back pain, percussion tenderness over the spine, and a rapidly evolving loss of motor and sensory functions. Whereas S aureus is the most frequent causative organism (see Chapter 46), aerobic and anaerobic streptococci, gram-negative bacilli, and a wide spectrum of other bacterial and fungal organisms have been shown to cause epidural abscesses. Thus, a premium should be put on obtaining pus from the abscess for culture and determination of the antimicrobial susceptibility of the causative organism. Until that information is available, initial therapy should be an intravenous penicillinase-resistant synthetic penicillin such as oxacillin or nafcillin in conjunction with rifampin. However, if there is a likelihood of a methicillin-resistant S aureus (MRSA) strain in the patient (eg, recent hospitalization in a unit with prevalent MRSA), vancomycin should be included in initial therapy and discontinued if the S aureus proves susceptible to oxacillin or nafcillin, which should then be the drugs of choice, in conjunction with rifampin.

Epidural abscess must always be considered in patients with back pain and rapidly evolving signs of cord compression. The presence of an obvious primary infection, with recent bacteremia (eg, recent incision and drainage of an abscess and/or fever) may be helpful in pointing to the diagnosis (and to the most likely organism), but these antecedent signs may be absent. Intravenous drug abuse is an increasingly frequent cause of epidural abscess.

The most frequent process mimicking an epidural abscess is cord compression from metastatic tumor. The diagnosis of these conditions is most easily made or excluded by a sagittal-screening MRI scan, which shows (for epidural abscess) a diffuse or multiloculated collection of pyogenic material compressing the cord over several segments, most often in the mid thoracic region; as the next most likely location, in the lumbar spine; and also, but least likely, the cervical spine. Rapid surgical intervention is necessary in most cases and certainly in all cases in which the neurological deficit is progressing.

Genital Herpes

Genital infection with herpes simplex virus (usually type 2) occasionally causes meningitis resulting in paraparesis, a dysfunction at the sensory level or a dysfunction in the bowel, the bladder, or both (see Chapter 33). A similar picture may occasionally be observed with segmental varicella-zoster infection. Whether these syndromes are caused by direct viral invasion of the spinal cord or an autoimmune-mediated myelopathy is unknown. A variety of viral illnesses such as mumps or chicken pox or vaccination procedures can cause a transverse myelitis, presumably by an immunologic reaction to CNS tissue triggered by the foreign antigen. The inciting agent in the majority of cases of acute transverse myelitis remains unknown. A chronic progressive myelopathy with ataxia, lightning-like pains, and later spastic weakness formerly was seen in tabes dorsalis but is rarely seen now. In contrast, HIV infection commonly causes a vacuolar myelopathy initially affecting the posterior columns; it presents with slowly progressive ataxia and culminates in a spastic paraparesis (see Chapter 23).


Essentials of Diagnosis

  • History: fever, headache, chills, sweats, malaise; focal neurological deficits—acute or subacute; infections in paranasal sinuses, mastoid, or elsewhere; intravenous drug use.
  • Signs: Fever, leukocytosis; heart murmur; focal neurological deficits.
  • Laboratory studies: MRI imaging; lumbar puncture, if not contraindicated by papilledema or presence of a mass lesion on MRI scanning; blood cultures, where appropriate.

The presence of fever, headache, focal neurological deficits, alterations of mental status, seizures, or some combination of these features suggests both focal disturbance of brain parenchyma and meningeal irritation. The range of conditions that can produce these disorders is large. Among the noninfectious causes, one must consider cerebrovascular disorders and primary or metastatic cancer as leading possibilities. In approaching such problems, it is important to try to determine the precise tempo of progression of the problem (ie, did the symptoms appear and become maximal in seconds to minutes, over a few hours, or over days?). Apoplectic onset or a seizure suggests an embolic process, whereas the development of a deficit over minutes to hours is more consistent with thrombosis or hemorrhage. Slower developing deficits suggest the growth of a mass lesion or sequential vascular insults which become additive.


Bacterial Endocarditis

The neurological complications of bacterial endocarditis are multiple, but the most frequent are those due to multiple emboli with infarction of the brain. Although larger emboli can cause obvious strokelike syndromes (most often in middle cerebral artery distribution), multiple smaller emboli may produce complex confusion states admixed with lesser degrees of focal disturbance. Brain abscesses, although infrequent in endocarditis, are usually associated with S aureus endocarditis and, if present in endocarditis, are usually small. They usually resolve with antimicrobial therapy alone. The formation of mycotic aneurysms at the site of embolism is not uncommon and may occur late in the course of the condition. As noted above, rupture of such aneurysms may be fatal.

One must be alert to the possibility of bacterial endocarditis in any patient with known congenital or acquired alteration of the heart valves, particularly if there has been recent oral or urogenital surgery or intravenous drug use. The traditional signs and symptoms of subacute bacterial endocarditis include asthenia, arthralgias, myalgia, anorexia, heart murmurs, splenomegaly, Roth spots, clubbing, fever, and sweats. Most such cases were caused, in the preantibiotic days, by oral streptococci, which have intrinsically low virulence, infecting heart valves damaged by rheumatic fever and causing small vegetations. However, such cases are now less prevalent and, with increasing intravenous drug use, S aureus, which can infect normal heart valves, is an increasingly prevalent cause of endocarditis. S aureus causes “acute” endocarditis with large vegetations, which embolize to cause metastatic abscesses, Osler's nodes, and, a much more toxic appearance than is typical of subacute endocarditis. The metastatic abscesses in staphylococcal endocarditis often occur in the brain and other parts of the CNS, so that the first presentation of endocarditis is often (20–40%) with stroke or another neurologic problem. The signs of endocarditis may all be easily overlooked, and the cause of the neurologic dysfunction missed if attention is devoted exclusively to the neurological phenomena. Thus, fever in the patient with neurologic findings should prompt a search for signs and symptoms of endocarditis, outlined above. The diagnostic criteria have recently been codified by Durack et al (1994). Once endocarditis is suspected, the most sensitive and specific diagnostic study is the transesophageal echocardiogram (ECHO). Repeated blood cultures may be required to identify the causative organism, but identification of the infecting microorganism and quantitative determination of its susceptibility to antibiotics are of critical importance in determining the nature and duration of treatment with intravenous antibiotics.

Herpes Simplex Virus-Induced Encephalitis

Encephalitides caused by viral infection of the brain frequently result in acutely or subacutely developing syndromes that combine headache, fever, alterations of mental status, seizures, and focal deficits. The most frequent cause of sporadic viral encephalitis is herpes simplex virus (HSV). The process in neonates is most frequently due to HSV type 2 (HSV2) resulting from maternal genital infection that was present at the time of birth. In children or adults, the encephalitic process is almost always caused by type 1 HSV (HSV1). Whether the brain infection results from exogenously acquired virus or from virus resident in cranial sensory ganglia or in the brain has not been determined.

In children or adults, the process usually takes place over a few hours to days. Initially the patient may exhibit behavioral changes or loss of memory or occasionally may complain of unusual olfactory or gustatory sensations. If present, these are valuable hints that herpes encephalitis should be considered. These symptoms may be followed by the development of headache, fever, focal deficits (hemiparesis or aphasia), and progressive disturbance of consciousness. Signs of meningeal irritation (stiff neck or vomiting) are often lacking. The diagnosis is most easily established by an MRI scan combined with typical CSF changes. The MRI scan is more sensitive than a CT scan for detecting HSV1 encephalitis; CT scans often appear normal during the first several days of the illness (when therapy is likely to have the greatest impact). Abnormalities on an MRI scan typically consist of contrast-enhancing lesions (bright on T-2–weighted images) in the medial temporal lobe and inferior frontal lobe, often extending medially and upwards into the putamen. Occasionally a seemingly separate area of disease is present in the cingulate gyrus.

The lesions are often associated with cerebral edema, and they are often bilateral, though rarely symmetrical. In our experience the lesions of HSV may be mimicked by cerebrovascular lesions in the temporal lobe or by the lesions associated with mitochondrial encephalopathies. The CSF is abnormal with a lymphocytic pleocytosis and moderately elevated protein concentration. The presence or absence of erythrocytes in the CSF is not of diagnostic help. Use of the HSV1 PCR to detect the presence of HSV genomes in CSF is generally very sensitive and highly specific, and this method has generally supplanted brain biopsy for diagnosis. The test may be falsely negative on the first day or two of the illness and after the second week. Tests for HSV antibody in the CSF are rarely positive early in the disease; cultures for HSV are almost always negative. The electroencephalogram may point to the presence of a temporal lobe abnormality; however, it is not highly specific for HSV infection. Nonetheless, a normal electroencephalogram weighs against a diagnosis of HSV encephalitis.

Treatment with intravenous acyclovir should be instituted as soon as the diagnosis is suspected, because delay in treatment is associated with a poorer outcome. With early, specific therapy, the mortality and morbidity are substantially reduced, and there is little risk from the drug except in patients with renal failure.

Arbovirus-Induced Encephalitis

A variety of arthropod-borne viruses (togaviruses) cause encephalitis, often in localized outbreaks associated with summertime increases in mosquito populations. The treatment of these encephalitides requires excellent supportive care until the patients improve on their own; there are no currently available specific antiviral compounds that are effective against arboviruses.

Brain Abscesses

A variety of bacterial infections must be considered in producing the brain abscess symptom complex. Brain abscesses commonly cause seizures, focal deficits, and, as they enlarge, progressive obtundation. Although many patients with brain abscesses have no evident primary source of infection, it is imperative to search carefully for a primary focus in the paranasal or mastoid sinuses with contiguous spread to the brain. These sites may yield the organism(s) causing the brain abscess. Additionally, metastatic (or “hematogenous”) abscesses, ones seeded via the bloodstream, can arise from infection in skin or lung, by IV drug use, in association with endocarditis, or in association with dental procedures.

Brain abscesses are usually recognized by contrast-enhanced CT or MRI scans. The importance of performing CT or MRI scans with contrast enhancement when testing for brain abscesses is demonstrated in Figure 7-1. Brain abscesses may be confused with brain tumors but are usually more spherical with thinner walls; gas, if present, is a valuable diagnostic feature indicating their bacterial etiology. Brain abscesses are often associated with marked degrees of cerebral edema.

Management of patients who have brain abscesses usually involves a combination of surgery for diagnosis and drainage or excision, antibiotic therapy, and treatment of cerebral edema. The bacterial flora causing brain abscesses are highly variable and are often composed of mixed aerobic and anaerobic bacteria. Staphylococci, anaerobic streptococci, and Bacteroides species predominate, but gram-negative bacilli may also be found in brain abscesses. Initial treatment should include a penicillinase-resistant penicillin such as nafcillin or oxacillin to treat a staphylococcal component, a third-generation cephalosporin for gram-negative organisms, and metronidazole for anaerobic streptococci and Bacteroides species. Some authors include an anti-Pseudomonas drug if the abscess complicates chronic otitis.

Stereotaxic surgical aspiration is advisable to establish bacteriologic diagnosis and is often useful to decompress large abscesses or abscesses that block or threaten to rupture into the ventricular system. Repeated aspirations may be necessary to control a mass effect. Abscesses tend to enlarge by extending toward the ventricular system, and they pose a risk for rupture into the ventricles with an often fatal outcome. Thus, drainage efforts must be especially vigorous with abscesses enlarging toward the ventricular surfaces. Extirpation of abscesses should be considered when they are solitary, well encapsulated, and surgically accessible. Surgical extirpation should be considered for posterior fossa abscesses because of their propensity to compress the brainstem and to obstruct the ventricular system.

Management of the cerebral edema that accompanies brain abscesses should include dexamethasone administered intravenously. Mannitol may be used, especially as a temporizing measure prior to surgical drainage. Note that the cessation of steroid therapy, used to diminish cerebral edema, may allow an increase in the inflammatory component of the abscess, with a resulting increase in the degree of enhancement of the abscess wall on contrast-enhanced CT scans. This phenomenon may unnecessarily raise alarm that the abscess is not yielding to therapy; but this conclusion may be erroneous in the face of steroid withdrawal.

Subdural Empyemas

Abscesses in the subdural space (subdural empyemas) are often associated with frontal, sphenoid, or ethmoid sinus infection. For reasons that are not understood, these empyemas are seen almost exclusively in males. Because the subdural space is continuous over the entire surface of the brain and between the hemispheres, large amounts of pus can be contained within it, causing widespread irritation and edema of the underlying brain. The organisms responsible are similar to those in brain abscesses, with aerobic streptococci, anaerobic streptococci, S aureus, and Bacteroides species predominating. In addition, S pneumoniae and H influenzae may cause these empyemas. Often there is associated meningitis if organisms and/or cells spread through the arachnoid into the subarachnoid space. In addition, involvement of cortical veins and venous sinuses in the inflammatory process and possibly with associated thrombosis can be seen.

Seizures are common. Because the CSF is usually abnormal and under raised pressure in these cases, the hazard of a spinal tap often outweighs the potential value of the information that can be gained. The diagnosis is most readily established by MRI or CT scan with contrast enhancement. The treatment consists of prompt surgical drainage through bilateral or multiple burr holes or by means of formal craniotomy. Provisional antibiotic choices can then be modified on the basis of Gram staining and culture of the aspirated pus.

Cerebral Venous Sinus Infections

Infections of the cerebral venous sinuses can be seen in association with any of the above purulent infections (meningitis, brain abscess, or subdural empyema) or as a consequence of mastoid or sinus infection. Usually the venous sinus involved is contiguous to an infected structure such as an infected sinus. The lateral venous sinuses thus may be involved when there is mastoid or ear infection, and cavernous sinus thrombosis may be associated with ethmoid or sphenoid sinus infection or with facial cellulitis. With extension of infective thrombus into cortical veins, seizures and cortical venous infarction are common. Infections of the cavernous sinus may produce proptosis and chemosis of the eye and palsies of the third, fourth, and sixth cranial nerves because these nerves traverse the cavernous sinus. This constellation of signs is also seen in diabetics with nasal or sinus infection caused by Mucor or Rhizopus fungal species. Involvement of the superior sagittal sinus frequently produces cortical vein thrombosis with seizures and may result in infection of the upper convexities of the brain with consequent leg paralysis.

The diagnosis of thrombosis of these venous structures is best made by MRI scanning, which can demonstrate the presence or absence of flow voids, clotted blood, engorgement of these structures, or some combination of these findings. The diagnostic certainty can be further enhanced by the use of magnetic resonance venography.

Treatment consists of antibiotics as for the treatment of brain abscesses or for other specific causative microorganisms that may be identified. Consideration should be given to administration of anticoagulants to inhibit the propagation of clots within the venous sinuses. However, the use of anticoagulants must be weighed against the possibility of worsening the process by hemorrhage, accompanying venous occlusion and infarction of brain.

Fungal Infections

Fungi may cause focal disease in the brain with a constellation of signs and symptoms similar to those considered above. Fungal infections are most often encountered in hosts with compromised cell-mediated and other types of immunity. They are thus seen more often in patients with AIDS, lymphoma, Hodgkin's disease, leukemia, or advanced diabetes or in patients receiving cytotoxic or immunosuppressive regimens. Cryptococcal infection usually presents as severe meningitis and should be considered in the differential of acute bacterial meningitides discussed earlier. Infection caused by Mucor or Rhizopus species occurs most frequently in diabetics with multiple episodes of acidosis. The infection may spread from the oropharynx or paranasal sinuses into the skull base, involving the orbit, cranial nerves two through six, and the cavernous sinus as well as the carotid artery. The clinical picture of a red or proptotic eye with third or sixth nerve paralysis in a diabetic should prompt aggressive biopsy and culture of affected tissues as well as culturing of the nasopharynx and sinuses for Mucor or Rhizopus species. Optimal management requires a combination of surgical debridement and therapy with high-dose amphotericin B or lipid-formulated amphotericin B.

The most frequent fungi associated with parenchymal infection of brain are Aspergillus and Candida species. These infections are seen most frequently in immunocompromised hosts, particularly in those with neutropenia. Aspergillus infections usually have their origins in pulmonary or sinus infections whereas Candida infections are often seen in patients with indwelling intravenous lines, in intravenous drug users, or in patients who have previously been treated with corticosteroids or broad-spectrum antibiotics.

These organisms, especially Aspergillus and Mucor or Rhizopus species, share a predilection for invading the walls of cerebral blood vessels with resulting thrombosis of the blood vessel. Thus, in addition to causing cerebral abscesses and meningitis, they often produce strokelike events as a result of thrombi forming in inflamed vessels. Treatment of these fungal infections is with high-dose amphotericin B or lipid-formulated amphotericin B. Therapy for Candidainfection is amphotericin B or lipid-formulated amphotericin B with or without 5-fluorocytosine, depending on the patient's underlying disease and the species of the Candida strain (some strains of certain species of Candida, such as parapsilosis, are exquisitely susceptible to the synergism of amphotericin B with 5-fluorocytosine).


Toxoplasmosis in the CNS presents most commonly with multifocal lesions, causing focal deficits, seizures, and impairment of cognitive functions over a period of days to weeks. Before the advent of AIDS, CNS toxoplasmosis was encountered only rarely, and then usually in the setting of Hodgkin's disease, lymphoma, or other states of severe immunosuppression. It has become a frequent complication in AIDS patients and should be immediately considered in the AIDS patient who develops multifocal neurologic deficits over a period of a few days to weeks.

The disease is often easily visualized by contrast-enhanced CT or (preferably) MRI scans, most often appearing as multicentric solid or ringlike enhancing lesions in the brain; the appearances are often quite characteristic but can be mimicked by cerebral lymphoma, also an AIDS-associated condition. A negative immunoglobulin G antibody test for Toxoplasma gondii makes the diagnosis unlikely. If the immunoglobulin G antibody test is positive, some experts advocate a therapeutic trial of sulfadiazine pyrimethamine, and folinic acid, in association with monitoring the clinical course as well as the size of the cerebral lesions on MRI scan. If there is no response in 10–14 days or if there is deterioration, a brain biopsy to examine other diagnostic possibilities should be strongly considered.


Essentials of Diagnosis

  • History: antecedent meningeal infection; infections of paranasal sinuses or skull base.
  • Signs: cranial nerve deficits, especially nerves two, four, five, six, and seven.
  • Laboratory: evidence of meningeal infection in CSF studies; MRI imaging of skull base and paranasal sinuses showing signs of an inflammatory process.

Involvement of the cranial nerves by infectious processes is usually the result of infection in the subarachnoid space at the base of the brain or in structures at the base near or through which cranial nerves course (eg, the cavernous sinus, as discussed previously). In the differential diagnosis, one must be aware that cranial nerves are also commonly involved by neoplastic processes, by inflammatory processes of other types (eg, sarcoidosis), or by vasculitic diseases, especially those affecting medium and small size vessels (eg, giant cell arteritis, polyarteritis nodosa, and diabetes mellitus).

Involvement of cranial nerves three, four, and six and the first division of five can be seen together because they traverse the cavernous sinus. Thus infections or infective thrombosis in the cavernous sinus can involve these nerves together.

Any meningeal infection, particularly if prolonged, can involve the cranial nerves at the base of the brain, so that palsies, particularly of the third, sixth, seventh, and eighth cranial nerves, can be seen in the course of pyogenic meningitis of any type or in more slowly evolving meningitides caused by tuberculosis, fungal infections, syphilis, or Lyme disease. Lyme disease seems to have a particular affinity for the seventh nerve; unilateral or bilateral facial paralysis is commonly seen. Involvement of the fifth nerve can be seen from reactivation of varicella-zoster virus in the trigeminal ganglion producing the well-known shingles eruption in one or more divisions of the nerve. Involvement of the intracranial portion of the carotid artery may occur in the course of ophthalmic zoster with thrombosis of the vessel and a middle cerebral distribution stroke. In contrast, reactivation of HSV in the same ganglion usually results only in the production of fever blisters on the lip.

The common Bell's palsy involving the facial nerve is tenuously associated with herpes simplex infections, prompting some authorities to recommend treatment of such cases with acyclovir. Involvement of the facial nerve by varicella results in the Ramsey-Hunt syndrome, with the appearance of vesicles in the ear. The facial nerve is susceptible to a variety of infections; in addition to those mentioned above, it is vulnerable to bacterial infections in the petrous apex. It, along with the eighth nerve, can be involved in Pseudomonas infections of the ear in diabetics (malignant external otitis).


Involvement of cranial nerves nine through twelve is less frequent in meningeal infections, perhaps because their dysfunctions are less obvious, and they are less carefully examined. Involvement of their nuclei in the brainstem is, however, common in polio, leading to severe dysphagia, dysarthria, and respiratory difficulties. Thus, polio must be considered in unvaccinated individuals who have traveled abroad.

Botulism & Pseudobotulism

Although botulism is a disorder of the neuromuscular junction rather than peripheral nerves, patients with botulism commonly present with dry mouth, dysarthria, dysphagia, diplopia, and impaired ocular accommodation. Rapid recognition of this disease is important. Prompt administration of antitoxin along with ventilatory support is essential in the management of botulism. In addition, recognition of the disease should prompt an intensive search for contaminated foodstuffs, which are most often the cause of the condition in adults. Victims who have only early symptoms may be recognized only because they were identified as sharing certain foodstuffs with individuals who have clear-cut disease.

A cluster of signs and symptoms similar to those in botulism may occur after ingestion of any part of the plant, Jimson weed (Datura stramonium); the syndrome may mimic botulism in patients who present with dysphagia; dilated, fixed pupils; and dry mouth (pseudobotulism), which is often accompanied by visual or auditory hallucinations. The Datura plant contains the anticholinergics atropine and scopolamine, which are highly concentrated in the seeds and can cause serious illness or death. Teenagers seeking mind-altering experiences sometimes experiment with Datura, only to die, probably from the cardiotoxic principle in the plant. They usually present with the pseudobotulism syndrome (fixed, dilated pupils and dry mouth), which is distinguishable from true botulism primarily by the history of contact with the Daturaplant or its seeds and by the hallucinations, which are not a feature of true botulism. If the cardiovascular system is stable, the patients usually improve over time without therapy, other than emptying the stomach, using activated charcoal, or both; however, if the patients manifest profound toxicity, including bradycardia or tachycardia, the use of the antidote physostigmine should be considered.

Datura poisoning might also suggest rabies to the initial observer, if the hallucinations are mistaken for encephalopathy and if the dysphagia is mistaken for hydrophobia.


Rabies should also be considered in the differential diagnosis of patients presenting with dysphagia and dysarthria, with or without hydrophobia and laryngeal spasms. Rabies must be considered in any patient who has traveled to third-world countries and who has had any contact with potentially infected animals. Skunks, raccoons, and bats are the main animal reservoirs of rabies in the United States.

Treatment with human immune globulin and diploid cell-derived vaccine is very effective for individuals exposed to or bitten by rabid animals, but it is ineffective once neurological symptoms have developed. It is important for persons in close contact with the victims, whose body fluids may be infectious or for others who have had contact with the same or other infected animals to receive postexposure prophylaxis. A detailed review of the indications and procedures for postexposure prophylaxis has been provided by the Centers for Disease Control and Prevention (CDC/MMWR, 1999).


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