Infections of the Central Nervous System

I. Case presentation
    A. Questions
    B. Case notes
    C. More cases
II. Syndromes of CNS  infection, causes and treatment
    A. Terminology
    B. Acute bacterial (septic) meningitis
    C. Viral (aseptic) meningitis
    D. Chronic meningitis
    E. Encephalitis
    F. Brain abscess and empyema
    G. Myelitis and spinal epidural abscess
    H. A slide show of organisms causing meningitis
III. Lumbar puncture
IV. References
V. Quiz
VI. Abbreviations
VII. About this page

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I. Case presentation

Chief complaint: Headache
History of present illness: This is a 35 year old man with headache (1). His headache began 3 weeks ago, and has occurred episodically since then. It has a pounding quality, is localized to both frontal areas, and is not associated with nausea, vomiting, or light-sensitivity. It is relieved by over-the-counter analgesics. He has had no changes in his vision (2). The patient has no previous history of similar headaches, and he has no family history of intractable headaches. He has suffered two episodes of impaired consciousness (3). The first was two weeks ago; he vomited once, then "passed out" for a few seconds. No jerking of the limbs or incontinence was observed. Later, he had a similar spell while driving his car.
Past medical history: Hypertension
Physical examination:
    Vital Signs T: 97.1 P: 80 R:20 BP: 157/77
    General physical exam: normal. Neck: supple.
    Neurological exam: MMSE: 28/30. CN: PERRL, EOMI, visual fields full to confrontation. Visual acuity: OS 20/25; OD 20/30. Funduscopy: bilateral papilledema, L retinal hemorrhage (4). Motor: normal muscle tone and strength all muscles tested. Sensory: normal. DTRs: brisk and symmetrical throughout. Babinski's sign: negative. Coordination: normal. Station and gait: normal.
    Laboratory studies: Toxicology screen, electrolytes, and ECG were normal. Head CT: normal. Head MRI: no ventricular enlargement. EEG: normal.
    Course of illness: He was hospitalized and the above tests were performed. He was treated with tramadol (Ultram®) for pain and amlodipine (Norvasc®) for high blood pressure. A lumbar puncture was done: opening pressure was greater than 450 mm of water. Cell counts were WBC 213 RBC 46. Differential: segs 1 bands 0 lymphs 81 monos 18. Protein 75. Glucose 24. CSF cryptococcal antigen was positive.

A. Questions

  1. What are two possible mechanisms of the patient's headache?
  2. How might the patient's increased intracranial pressure be treated?
  3. What is the possible significance of the patient's episodes of loss of consciousness?
  4. What is the most common fungal infection of the CNS?
  5. What antibiotic treatments are used for cryptococcal meningitis?
  6. What illnesses or therapies predispose to cryptococcal meningitis?

B. Case notes

(1) Headache
Headache is the most common complaint of patients in a general neurology practice. The large majority of headaches are not life-threatening, and are due to migraine, tension, or chronic daily headaches. A small number have serious underlying causes: space-occupying intracranial lesions such as neoplasm or abscess, subarachnoid hemorrhage, hydrocephalus, meningitis, or encephalitis.

(2) Headache symptoms
Migraine headache is the most common type of headache for which patients seek medical treatment. Diagnosis is purely clinical--there is no laboratory test. Migraine headache is more common in women than in men, and there is often a family history of migraine. The essential symptoms of migraine headache are severe, throbbing headache with nausea. Other common symptoms include unilateral headache, photophobia, and phonophobia. The patient usually wants to lie down in a dark room, and if she can go to sleep, feels better on awakening.
    In migraine with aura the headache is preceded by visual symptoms. This may be as nondescript as vague black spots, or as dramatic as  "scintillating scotoma" or "fortification spectra"--brightly colored images with jagged lines. When clearly present, visual symptoms are invaluable for diagnosing migraine.
    Cluster headache is less common. The pain is nonthrobbing, unilateral, and retroorbital. An individual headache is brief, but recurs frequently, and the pain is said to be the most intense of all headache pain.
    Tension headache is very common, but not usually a cause for visits to the doctor's office. The pain is moderate, usually non-throbbing, and tends to be localized to the neck, occiput, and temples.
    Headache pain due to serious causes is variable. Most patients with intracranial neoplasm have a mild headache, not usually severe enough to seek medical attention. When present, it has symptoms reminiscent of tension headache, but it may worsen at night and awaken the patient from sleep. Patients with subarachnoid hemorrhage have a severe headache of sudden onset, often associated with temporary confusion and meningismus. Patients with bacterial meningitis often have a migraine-like headache with severe throbbing, nausea, and photophobia. Headache in pseudotumor cerebri is variable, but may have migraine-like qualities, and is often associated with transient blurring of vision that can, to the unwary, suggest migraine.

(3) Impaired consciousness
Sudden onset of impaired or loss of consciousness has two main causes: syncope and seizure.
    Syncope due to fall in blood pressure is most common. It may be preceded by a feeling of lightheadedness, as in orthostatic hypotension, vasovagal syncope, or vasodepressor syncope, or there may be no warning at all, as in sudden ventricular fibrillation. Onset in vasovagal or vasodepressor syncope is usually slow, and the patient may be able to remember the characteristic symptoms of lightheadedness followed by blindness prior to loss of consciousness. When consciousness is lost the patient collapses and falls. Usually there is quick recovery once the patient is recumbent, and there is no post-syncope confusion.
    The cause of loss of consciousness in syncope is global cerebral hypoperfusion--blood pressure drops, so the entire brain becomes ischemic for a brief time. Syncope is not due to primary brain disease, but if the hypoperfusion is prolonged for more than two minutes irreversible brain damage begins to occur.
    Seizure is also common. A generalized tonic-clonic convulsion is usually easy to diagnose from the history. A complex partial seizure is more difficult to diagnose. There often is a sudden alteration of consciousness, unresponsiveness, often with purposeless repetitive behaviors, followed by postictal confusion.
    Seizures are caused by the sudden onset of paroxysmal synchronous firing of neurons. Generalized seizures can be a symptom of a metabolic abnormality that only secondarily affects brain. Partial-onset seizures strongly suggest a specific abnormality of cerebral cortex.
    Increased intracranial pressure can cause syncope if the increase is large and sudden. Acute hydrocephalus, such as may occur with shunt malfunction or intermittent obstruction of the third cerebral ventricle due to "ball valve" tumors, may cause this. Loss of consciousness occurs in subarachnoid hemorrhage due to berry aneurysm because aneurysmal rupture causes intracranial pressure to temporarily equal arterial pressure, thereby reducing cerebral perfusion pressure to zero.

(4) Papilledema and increased intracranial pressure
The rigid skull makes the volume of the intracranial space constant. The major intracranial contents are:

  1. Brain parenchyma
  2. Cerebral spinal fluid
  3. Blood, venous and arterial
These, like water, are incompressible. An increase in the volume of one of these, or the presence of a space-occupying lesion, must produce a pressure increase, and will be compensated for by a decrease in the volume of one of the other compartments.
     Signs and symptoms of increased intracranial pressure may include:
  1. Bulging fontanelle (infants)
  2. Large head (infants)
  3. Nausea
  4. Projectile vomiting
  5. Headache
  6. Reduced retinal venous pulsations
  7. Papilledema
  8. Cranial nerve VI palsy
  9. Bradycardia (severe cases)
    The headache of increased intracranial pressure (ICP) is not distinctive. Projectile vomiting--sudden forceful vomiting without preceding nausea--is distinctive, but not often seen.
    The signs of increased intracranial pressure may be very helpful for diagnosis. An early and sensitive sign is venous engorgement and loss of retinal venous pulsations. When the pressure is normal, pulsations can be observed in retinal veins. If venous pulsations can be seen, it implies that intracranial pressure is 250 mm of water or less [21]. Since pulsations may be difficult to observe, and are absent in 25% of normal people, this sign is more helpful for ruling out high ICP than for demonstrating its presence.
venous pulsations
Figure 1. Venous pulsations

    Venous engorgement and loss of pulsations occur because the central retinal vein drains into the cerebral circulation, so its pressure increases when ICP increases.
    Papilledema implies swelling of the optic disk. Features to look for with the direct ophthalmoscope are:

  1. Blurring of the optic disk margins, especially the nasal margin
  2. Loss of the optic cup
  3. Engorgement of retinal veins
  4. Obscuration of vessels passing through the disk margin
  5. Flame-shaped hemorrhages in the nerve fiber layer
normal optic disk papilledema
Figure 2. Normal optic disk Figure 3. Papilledema
    Edema of the optic nerve head in papilledema is caused by disruption of fast axoplasmic transport. Axonal material "piles up" at the optic nerve head. It is thought that papilledema can become apparent within about six hours of an acute increase in ICP.
    Even when its appearance is dramatic, papilledema does not produce (initially) diminished vision. If increased ICP does cause diminished vision, the increase must have been severe and chronic, and a more likely ophthalmoscopic finding is optic atrophy due to degeneration of the nerve. In cases in which the optic nerve head is clearly swollen, and vision on the affected side is clearly diminished, a more likely condition is papillitis. This may be seen in acute optic neuritis, or in anterior ischemic optic neuropathy. In these conditions the papillitis is usually unilateral.
    Another non-specific sign of increased ICP is palsy of cranial nerve VI. When bilateral cranial nerve VI palsy occurs in the absence of other findings, increased ICP is strongly suggested. The presumed mechanism of cranial nerve VI palsy with increased ICP is traction on the nerve. The sixth nerve takes a long course from its origin at the pontomedullary junction upward over the wing of the sphenoid bone, and from there to the cavernous sinus. It may necrose at the point it leaves the subarachnoid space [20].
cranial nerve VI cranial nerve VI palsy
Figure 4. Cranial nerve VI Figure 5. Bilateral VIth nerve palsies

C. More cases

Select a case to study.
  1. Case 2: an infant with fever
  2. Case 3: a man with headache

II. Syndromes of CNS infection, causes and treatment

A. Terminology

An infection of the central nervous system may primarily affect its coverings, which is called meningitis. It may affect the brain parenchyma, called encephalitis, or affect the spinal cord, called myelitis. A patient may have more than one affected area, and if all are affected, the patient has "meningoencephalomyelitis". The nervous system may also suffer from localized pockets of infection. Within the brain or spinal cord there may be an abscess, and outside them there may be an epidural abscess or subdural empyema.

B. Acute bacterial (septic) meningitis

Signs and symptoms

Early in the course of the illness, the patient with a purely meningeal infection will be awake, and painfully aware of his symptoms, so you may simply ask him about them. Later in the illness, if untreated, the meningeal inflammation will have led to diffuse brain dysfunction, ischemia or infarction, and the patient will be stuporous.
    The classic signs of meningeal infection are fever, stiff neck (meningismus), and headache. Although characteristic of meningitis, headache and meningismus may occur in other infections, such as pneumonia. Photophobia, nausea, vomiting, malaise and lethargy are common. The latter are also common in "functional" headaches like migraine, and may confuse the unwary physician.

Meningeal signs

The stiff neck that occurs in meningitis is often striking--it is really stiff, almost boardlike, but not so painful as it is stiff. The stiffness is caused by reflex spasm of the neck muscles due to traction on inflamed cervical nerve roots. It is greatest with flexion, less with extension or rotation. Of course, a lot of older people have necks that are quite stiff due to osteoarthritis, and if they have a fever, this may occasionally lead to diagnostic concern for meningitis. Usually their necks are stiff with both rotational and flexion/extension movement. Associated with the stiff neck are two other classic "meningeal signs", the signs of Kernig and Brudzinski. Brudzinski's sign is involuntary flexion of the hip and knee when the examiner flexes the patient's neck. Kernig's sign is limitation of straightening of the leg with the hip flexed. Meningeal signs occur not only in infectious meningitis, but in subarachnoid hemorrage and chemical meningitis. Unfortunately, meningismus occurs only in about 50% of cases of bacterial meningits, so the sign is neither highly specific nor highly sensitive.


  1. Suspicious clinical symptoms and signs.
  2. CT of head to rule out abscess or other space-occupying lesion, if it can be done quickly.
  3. Lumbar puncture (see below).
  4. Blood cultures.

Causes and therapy

Streptococcus pneumoniae
This organism is now the most common cause of bacterial meningitis in all age groups except newborns. It is a Gram-positive coccus that occurs in pairs (Click for micrograph [83k]). It has an external polysaccharide capsule that determines its serotype. Serotype is important for vaccine creation and epidemiology, but is not routinely performed on clinical isolates, and does not guide antibiotic therapy.
    The nasopharynx is the primary site of pneumococcal colonization; 5 to 10% of healthy adults and 20-40% of healthy children carry at least one strain of S. pneumoniae, with higher incidences in winter [7]. Spread is from person to person through droplets, so there is an increased chance of spread in day care centers, barracks and prisons. It is a serious illness, with a case mortality rate of 21% [1].
    The organism may spread to the meninges through local extension from an infected sinus or middle ear infection. Because it colonizes the nasopharynx this strain is common when meningitis occurs as a consequence of ENT procedures or of chronic CSF leak.
    Major risk factors for meningitis with this organism are: splenectomy, diabetes mellitus, liver disease, alcoholism, CSF leak, terminal complement deficiency, and pneumococcal pneumonia. Recently, coclear implant has been found to be a risk factor [22,23].

    Treatment and prevention
For many years, S. pneumoniae was reliably sensitive to penicillin. Meningitis caused by these strains responds to meningitis doses of penicillin, ampicillin, cefotaxime, or ceftriaxone.
    In recent years, penicillin-resistant strains have become common, and these constitute about 30% of cases in Springfield, Illinois. For the most part these strains remain susceptible to the third generation cephalosporins ceftriaxone and cefotaxime, which enter CSF in good concentrations [25]. For meningitis, a third-generation cephalosporin plus vancomycin is usually recommended for intial therapy until culture and sensitivity is available. No vancomycin-resistant strains have yet been documented, but vancomycin is not used alone because of its poor penetration into the CSF. There is some concern that dexamethasone may reduce blood brain barrier permeability to antibiotics. Because the organism is sensitive to rifampin, which easily passes the blood brain barrier, the addition of rifampin has been suggested [24].
    Like pneumococcal pneumonia, meningitis can be prevented with pneumococcal conjugate vaccine. In 2000, routine vaccination of children with pneumococcal vaccine was begin, but data are not yet available regarding changes in meningitis incidence. 

Hemophilus influenzae
H. influenzae is a small (1-2 micrometer diameter) Gram-negative coccobacillus (Click for micrograph [89k]). Strains causing meningitis in children almost all have an outer capsule, but non-meningitis-causing strains do not.
    The organism colonizes the upper respiratory tract of humans, who are its only natural host. Spread occurs through respiratory droplets or by direct contact with respiratory secretions. Risk factors for meningitis include head trauma, neurosurgery, paranasal sinusitis, otitis media and CSF leak.
    The case fatality rate for meningitis is approximately 6% [1] in children, higher in adults.

    Treatment and prevention
H. influenzae meningitis can be prevented by vaccination. Since the widespread use of H. influenzae conjugate vaccine in the 1990s, the incidence of H. influenzae meningitis has declined dramatically, with more than a 90% decline among children under 5 years old [2,3,4,1]. As with S. pneumoniae, beta-lactam and ampicillin-resistant strains are increasingly found, but resistance to ceftriaxone or cefotaxime are rare, and these are the drugs of choice.
    Rifampin is used for prophylactic chemotherapy to prevent secondary cases.

Listeria monocytogenes
Listeria monocytogenes is a facultatively anaerobic Gram-positive rod (Click for micrograph [137k]). The organism can be found in human feces, unpasteurized milk, cheeses, and other foods. Most cases are sporadic, and contaminated food is the source of infection. It may be difficult to diagnose clinically, because compared to other meningitides meningeal signs are less frequent, there is a lower CSF WBC count, less neutrophilic predominance, and lower protein [5,6]. Cranial nerve dysfunction may occur, and there are occasional cases of brainstem encephalitis [26].
    Listeria monocytogenes is a common cause of meningitis in infants less than 1 month old, and is also common in adults greater than 60 years old. Risk factors include pregnancy, advanced age, and immunosuppression. The case fatality rate for L. monocytogenes meningitis is 15% [1].

    Treatment and prevention
Listeria monocytogenes remains sensitive to penicillins, and ampicillin is the antibiotic of choice, but treatment must be prolonged--3 or 4 weeks. Trimethoprim-sulfamethoxasole is an alternative for the penicillin-allergic patient.
    Listeriosis results from food-borne transmission, so proper food handling measures markedly reduces infection risk.

Group B streptococcus
This is the most common meningitis in infants less than 1 month of age (70% of cases) (Click for micrograph [82k]). Transmission to the neonate usually occurs from mothers colonized by group B streptococcus in the genital tract. In adults, group B streptococcal infection is often nosocomial. The case fatality rate is 7%.

    Treatment and prevention
Beta-lactam-resistant strains of group B streptococcus have not emerged. Treatment is with penicillin and ampicillin. Neonatal meningitis can be prevented by therapies aimed at reducing maternal birth canal colonization, or by Caesarian section.

Neisseria meningitidis
Neisseria meningitidis is an encapsulated Gram-negative organism that appears in pairs on Gram stain (Click for micrograph [80k]). It commonly colonizes the nasopharynx, and can spread rapidly from person to person through respiratory droplets. N. meningitidis often occurs in epidemics among persons living in close quarters like dormitories or barracks.
    The course of the illness is usually rapid and dramatic. Initial non-specific fever, headache, and myalgia give way to distinctive signs of a petechial rash on the trunk and lower body that may coalesce into purpura [fifteen]. Septic shock, disseminated intravascular coagulation, and distal extremity necrosis may occur in disseminated meningococcemia. Although treatment is effective and the disease usually occurs in immunocompetent patients, nevertheless the case fatality rate is  3% [1] to 13% [five]. It is common to have non-lethal complications such as cutaneous scars, amputation, hearing loss, and renal injury.
    As with other encapsulated organisms, asplenia is a risk factor for infection.

    Treatment and prevention
Penicillin-resistant strains are uncommon, so drugs of choice are penicillin or ampicillin. Ceftriaxone or cefotaxime response is also excellent. A polysaccharide vaccine has been available for a number of years and routinely routinely recommended for all adolescents, such as college freshmen or military recruits. It has also been useful in patients with risk factors such as asplenia. Since 2005 a conjugate vaccine has been available [27], which should now be used instead of the polysaccharide vaccine.
    Close contacts of patients have a significantly increased risk of contracting infection, so antimicrobial prophylaxis is recommended for household members, day care contacts, and others. This should be done within 24 hours after exposure because secondary disease occurs within several days. For prophylaxis, rifampin is given twice daily for two days, but is contraindicated during pregnancy. One dose of ciprofloxacin or ceftriaxone is an alternative, and ceftriaxone can be given to pregnant patients.

Presumptive therapy for bacterial meningitis

Age Major pathogens Antibiotics
less than 3 months group B strep. ampicillin

E. coli + cefotaxime

L. monocytogenes

S. pneumoniae
3 months to 50 years S. pneumoniae 3rd generation cephalosporin (1)

N. meningitidis + vancomycin (2)

H. influenzae (now rare in USA)
greater than 50 years S. pneumoniae ampicillin
or impaired cellular immunity
L. monocytogenes + 3rd generation cephalosporin (3)

Gram (-) bacilli + vancomycin

(1) Ceftriaxone or cefotaxime
(2) Essential in areas with a high prevalence of penicillin-resistant S. pneumoniae.
(3) For patients with penicillin allergy, trimethoprim-sulfamethoxasole can substitute for ampicillin in treatment of L. monocytogenes.

Pathogen-specific therapy for bacterial meningitis

Organism Drug of choice (1) Second choice if allergic Duration of therapy
group B streptococci penicillin G or ampicillin vancomycin 14 - 21 days
H. influenzae 3rd generation cephalosporin chloramphenicol 7 - 10 days
L. monocytogenes ampicillin + gentamycin trimethoprim-sulfamethoxasole 14 - 21 days
N. meningitidis penicillin G or ampicillin chloramphenicol 7 - 10 days
S. pneumoniae (sensitive) penicillin G vancomycin + rifampin 10 -14 days
S. pneumoniae (resistant) 3rd generation cephalosporin + vancomycin vancomycin + rifampin 10 -14 days

(1) An infectious disease consultatant is always helpful in making these choices.

Adjuvant therapy

In a recent study of acute bacterial meningitis in adults, dexamethasone was shown to significantly reduce morbidity and mortality [19]. Results were best for S. pneumoniae, but no effect could be demonstrated for N. Meningitidis. Dexamethasone has been shown to reduce hearing loss in H. influenzae meningitis [17]. Dexamethasone should be given before or with the first dose of antibiotic, at a dose of 10 mg IV every 6 hours for 4 days for adults.


In meningitis of all kinds there is infiltration of the dura, arachnoid and pia mater with inflammatory cells. Conveniently, these spill over into the cerebrospinal fluid, allowing you to detect them with a lumbar puncture. If the condition were to affect only the meninges the condition would be bothersome, but no emergency. But that is not the case. Bacterial meningitis affects brain parenchyma in several ways: release of toxic bacterial products, stimulation of brain cytokine release, and frank brain infarction. Some toxic products of S. pneumoniae include pneumolysin, which forms pores in cell membranes, hydrogen peroxide, and bacterial cell wall. In the most serious meningitides, brain infarction occurs. Recall how the blood supply to brain is from large arteries located in the subarachnoid space. These give off small branches that project through the pia mater at what are called the Virchow-Robin spaces. Meningeal inflammation affects these vessels strongly, and the infection can spread to brain itself through the Virchow-Robin spaces. In bacterial meningitis this occurs within hours, and the condition is curable only if treated early, which makes bacterial meningitis a true medical emergency. You can sterilize the CSF at any stage of the disease, but you can't heal the brain damage, so the sooner the treatment the better.

C. Viral meningitis

Signs and symptoms

This is the most common kind of meningitis, and the most benign. A systemic viral syndrome may be present, but fever and headache may suggest meningitis. Nuchal rigidity is usually present. It is highly unusual for focal neurologic signs to occur.


Cerebrospinal fluid usually shows an "aseptic" picture--a lymphocytic pleocytosis with dozens to hundreds of WBCs, and normal glucose, protein and pressure. Viral culture may grow enterovirus, but is usually negative.

Causes and therapy

Enteroviruses are the major pathogens. These include echovirus, coxsackie A and B viruses, and polioviruses. Prior to widespread vaccination, mumps was a common cause of this illness. The course is benign, but the patient may have headache for several weeks.


Although uncomfortable, viral meningitis almost never leads to serious sequelae. However, early in the course of acute bacterial meningitis the patient may not be very ill, and the CSF may show only a lymphocytic pleocytosis, very much like that of aseptic meningitis [28]. Because aseptic meningitis may so closely resemble early acute bacterial meningitis, my usual tactic is to admit all meningitis patients to hospital for a day or two of observation, until lack of bacterial growth in CSF cultures confirms the meningitis is aseptic.

D. Chronic meningitis

Signs and symptoms

In general, symptoms develop slowly. Meningismus may be mild. There may be subtle mental status changes.


  1. This is a difficult diagnosis because signs and symptoms are often non-specific. It can be suspected in any patient with a chronic encephalopathy, or a patient with new onset of hydrocephalus.
  2. MRI or CT of head may show hydrocephalus or contrast enhancement of the basal meninges.
  3. Lumbar puncture.


There are a number of causes--bacterial, fungal, parasitic, and non-infectious. This is not a complete list, but includes organisms I have at least a little personal experience with:


Non-infectious: Mycobacterium tuberculosis
M. tuberculosis is an acid-fast bacillus. It is passed between persons through respiratory droplets. Mycobacteria multiply in alveolar spaces or macrophages, and within 2 to 4 weeks hematogenous spread to extrapulmonary sites occurs. From there, tubercles develop, and if brain tubercles rupture into subarachnoid space, meningitis develops. Deeper tubercles become tuberculomas.
    In tuberculous meningitis a thick exudate forms and involves blood vessels. Hence, complications of tuberculous meningitis include vasculitis, stroke, and border-zone encephalopathy. Obstruction to CSF flow may lead to hydrocephalus.
    Clinical features of tuberculous meningitis include fever, headache, meningismus and mental status changes. Vomiting and other signs of increased intracranial pressure may occur. Cranial nerve palsies due to involvement of the basal meninges or increased intracranial pressure occurs in approximately 25% of cases. In the U.S., HIV infection is a risk factor for tuberculous meningitis, and the clinical picture is similar. Other mycobacteria (M. avium, M. africanus) can produce human disease, and M. avium is an opportunistic pathogen in AIDS patients.
    Spinal cord may be involved by tuberculosis. Usually the thoracic cord is affected, and syringomyelia can be a late effect.  Tuberculous spondylitis may result in a psoas abscess or an epidural abscess.

    Cerebrospinal fluid
The CSF in tuberculous meningitis shows a lymphocytic pleocytosis with elevated protein and reduced glucose. Staining for mycobacteria is positive in 5 to 25%, and culture is positive in approximately 60% of cases. In some cases as many as four CSF examinations may be required to detect the organism, or it may be necessary to sample directly from ventricular fluid. CSF PCR may be useful.
    With treatment, the CSF returns to normal slowly. Glucose is the first to normalize, but it takes at least three weeks, and usually more [8].

Contrast-enhanced CT or MRI scans show a basilar meningitis, with contrast enhancement of the meninges in the suprasellar area, prepontine cistern, or interpeduncular fossa. Obstructive or communicating hydrocephalus may occur.

    Therapy is prolonged--isoniazid, rifampin and pyrazinamide daily for two months, then isoniazid and rifampin daily or twice weekly for four months [9]. Therapy may be even longer in patients who show a slow response.
    There is evidence that corticosteroids improve neurologic outcome [10].

    Prognosis and complications
Death occurs in 25% of cases. Complications of the disease include brain infarction in 25 to 40% due to involvement of perforating vessels at the base of brain. Infarction of the basal ganglia is especially common. Hyponatremia due to hypothalamic involvement may also occur.

Fungal infections
Depending on growth conditions, dimorphic fungi exist in a yeast (unicellular) form or in a filamentous (mold) form. In the filamentous form they have tubular structures called hyphae, which are divided into segments. Some segments have the ability to form spores.
    Most fungal infections begin with inhalation of spores, but may also come from indwelling catheters, mouth or GI tract (Candida), nasal sinuses (Aspergillus sp., Zygomycetes sp.) or skin (sporotrichosis).
    The most common organisms in CNS fungal infections are Cryptococcus neoformans (Click for micrographs [121k and 82k]), Coccidioides immitis, Histoplasma capsulatum, and Blastomycetes dermatididis. The clinical presentation is usually as a subacute or chronic meningitis, but fungal abscesses may also occur and cause focal neurologic signs.
    Risk factors include AIDS (Cryptococcus), organ transplantation  or diabetes (Aspergillus), or indwelling intravascular catheters (Candida). The likelihood of CNS disease is increased in the presence of systemic disease of kidney, lungs, or skin.

    Cerebrospinal fluid
The white blood cell count is usually moderately elevated, with 20 to 1000 cells per cu. mm. Lymphocytes usually predominate. Aspergillus, Blastomycetes, and Zygomycetes may cause a neutrophilic predominance, and Coccidioides may cause eosinophils to occur in the CSF. Special stains for fungi may demonstrate the organism.

    Cryptococcus neoformans, in addition to being the most common fungal meningitis, is the easiest to diagnose in the laboratory.  CSF culture for this organism, although growth is slow, is usually positive. For cryptococcus, a sensitive and specific test to detect capsular antigen is available and can be performed rapidly, so it is quite useful for clinical management. For initial diagnosis, test of the antigen in the CSF is most useful, but serum tests can be useful for following the course of therapy. The India ink test for cryptococcus, although quite specific, is not very sensitive, and no longer routinely performed by some laboratories.
    Antigen tests are not available for other fungi. Antibody tests are available, but immunosuppressed patients may not be able to mount a significant antibody response. PCR is not yet clinically available.

With Cryptococcus, diagnosis can usually be made from CSF studies. With other fungi, recovery of the organism from a non-CNS site such as skin, joint fluid, lung lesions, sinuses, bone marrow, urine, or blood is helpful. Often, brain biopsy is required. A diagnosis based on cultures from other body sites must be considered probable rather than definite.

The drug of choice for all fungal meningitides is amphotericin B, but it has several disadvantages. It must be given intravenously rather than PO because of poor gut absorption. It can be given intrathecally, but discomfort and toxicity are considerable with this route. It crosses the blood-brain barrier poorly and the dose that can be given is limited by renal toxicity. Intravenous doses cause a variety of unpleasant side effects including fever, chills, nausea, and vomiting, but adjunctive medications (diphenhydramine, ibuprofen, prochlorperazine) are used to control these symptoms. Life-threatening, but uncommon reactions include anaphylaxis, seizures, and cardiac effects. Drug treatment may have to be halted if rises in serum creatinine indicate renal toxicity. New lipid formulations of amphotericin B may reduce these toxicities.
    Fluconazole is also useful, and it can be given by mouth as well as intravenously, but the cure rate is lower than with amphotericin B. Fluconazole is standard for AIDS patients after a course of amphotericin is finished. Patients with C. neoformans, Candida sp., or Aspergillus sp. may also be given flucytosine, especially if the patient has AIDS.

Half or more of patients with fungal meningitis develop complications. Communicating hydrocephalus is common (5  to 10% with cryptococcal meningitis), and may result either from blockage of CSF flow within the basal cisterns, or in the arachnoid villi of the sagittal sinus. Arachnoiditis can cause obstructive hydrocephalus by blocking outflow from the IVth ventricle. Stroke, cranial nerve palsies, seizures, and encephalopathy can also occur.

Other causes of chronic meningitis

E. Encephalitis

Symptoms and signs

The patient with encephalitis is having problems with his brain, and likely with thinking, so he may not give you a good history. Family and friends may report the characteristic symptoms: personality change, lethargy, confusion, irritability. Focal neurologic signs are uncommon. The time course may be short in case of herpes simplex encephalitis (days), or much longer as in the case of Creutzfeld-Jakob disease (months). The only common acute encephalitis that is caused by herpes simplex virus. Its time course is relatively short, and fever, altered mental status and seizures are common. A triad of symptoms that should definitely bring it to mind is: fever, personality change, seizures. The only common chronic encephalitis in Illinois is HIV encephalitis.


  1. History and physical
  2. Brain imaging to rule out space occupying lesion
  3. Lumbar puncture
  4. Culture of CSF (some organisms)
  5. Acute and convalescent titers of antibody
  6. PCR of CSF for Herpes encephalitits
  7. Brain biopsy in exceptional cases


Herpes simplex virus
By far the most common sporadically-occuring encephalitis is that caused by herpes simplex virus (HSV). HSV-1 (herpes labialis) is most common in adults, with only 6 to 15% of cases caused by HSV-2 (genital herpes) [11], but HSV-2 is more common in neonates, who are infected by passing through mother's infected birth canal.
    Primary HSV-1 infection usually occurs in the mouth, and is asymptomatic. Symptoms later occur with painful lesions on the mucosa of the cheek or gums. After primary infection the virus establishes a latent infection in the trigeminal ganglion. Encephalitis may occur either during the primary infection or during reactivation of a latent infection.
    The clinical presentation includes fever, headache, and behavioral abnormalities or personality changes. Seizures and focal neurologic deficits often occur. Initial symptoms may be mild, so several days may elapse before the seriousness of the illness becomes apparent.
    HSV-1 encephalitis causes inflammation and necrosis in the temporal lobes and frontal cortex, which easily explains the tendency to cause seizures, personality change, and neurologic deficits.

MRI of the head shows T2-bright lesions in the medial and inferior temporal lobes. EEG may show nonspecific slowing, or may show periodic discharges in the temporal leads on one or both sides.
    CSF examination may show an increased opening pressure if there is significant brain swelling. There usually is a lymphocytic pleocytosis of 5 to 500 cells per cu. mm and a mildly elevated protein. Red cells and xanthochromia are usually present. CSF viral cultures are usually negative. PCR of CSF to detect HSV nucleic acid is useful, though in our laboratory the result returns too slowly to be useful in deciding whether to use antiviral therapy. In addition, the reaction is inhibited by RBCs, so false negative results can occur.
    Brain biopsy demonstrates Cowdry A intracellular inclusions, and is relatively sensitive and specific for the condition, but is not usually performed if a probable diagnosis can be made without it.

    Treatment and prevention
Intravenous acyclovir (10 mg/kg every 8 hours for 2-3 weeks) is standard. Rarely, HSV is resistant to acyclovir, and must be treated with foscarnet [12]. Neonatal HSV-2 encephalitis can be prevented by Caesarean section.

Arthropod-borne encephalitis
    West Nile Virus [18]
The West Nile Virus (WNV) first appeared in the U.S. in New York in 1999, and has since spread nationwide. In 2002, Illinois had the distinction of being the state with the most cases of WNV. In 2002 WNV was by far the most common etiology of viral encephalitis in the state. WNV's natural host is birds, especially crows and blue jays, and these animals develop a high titer viremia. It is transmitted from viremic birds to humans by Culex mosquitoes. Humans develop only low-level viremia, and human-to-human transmission by mosquitoes has not been documented. A few cases have been documented of WNV transmitted by blood transfusion, organ transplantation, breast feeding, by placental transmission, or by exposure of laboratory workers to infected sera or animals.
    The viral incubation period is 2 to 15 days. Most patients have an asymptomatic infection, but 20% will develop a fever, headache, backache, myalgia, and anorexia, lasting 3 to 6 days. About 50% develop a rash, and lympadenopathy can occur. About 1 in 150 infections will cause a severe illness with meningoencephalitis. Age is a strong risk factor, with the risk for 80 year olds almost 50-fold increased. Symptoms include flaccid weakness due to involvment of anterior horn cells, or less commonly parkinsonism, ataxia, polyradiculopathy, seizures, and cranial neuropathy. Mortality of the neurologic illness is about 10%, and recovery is rather poor in non-fatal cases.
    Radiologic findings are nonspecific. Diagnosis is based on clinical history, serology, and CSF findings. CSF shows a mild pleocytosis (30 - 100 cells/mm3), primarily lymphocytes, mild protein elevation, and normal glucose. Serologic tests are perfomed on both serum and CSF. WNV IgM is detectable in 90% of patients at 8 days, and persists for more than 6 months, so it is not an indicator of an acute infection. WNV IgM in the CSF indicates CNS infection. IgG antibodies increase between days 7 and 21.
    There is no specific treatment. Prevention relies on mosquito avoidance and control.

    Other arbovirides
The most common in the midwest U.S. are La Crosse virus and St. Louis encephalitis. They are transmitted by mosquitos and occur mainly in late summer and early fall. Symptoms are those of a flu-like illness, with evidence of brain involvement indicated by lethargy, confusion, irritability, tremors, or seizures. La Crosse virus may produce focal neurologic signs. St. Louis encephalitis may be associated with hyponatremia due to SIADH.
    CSF shows a lymphocytic pleocytosis. Diagnosis requires a fourfold rise in antibody titer between acute and convalescent sera, viral isolation from CSF, or demonstration of IgM antibody in CSF.
    Treatment is merely supportive--no specific antiviral therapy is available.

Other causes of encephalitis
Primary infection of meninges or brain by human immunodeficiency virus (HIV) is common, and causes meningitis or encephalopathy.  Rabies virus encephalitis is very rare, and almost invariably fatal. It can be prevented by immunization after exposure to a rabies-infected animal. In the immunosuppressed patient, varicella-zoster virus, Epstein-Barr virus, human herpes virus type 6, cytomegalovirus, measles and enterovirus can all occasionally cause encephalitis.



HSV is the most common cause of sporadic encephalitis. An effective, safe treatment for it exists, but not for other infections, so many patients with encephalitis are treated presumptively with acyclovir.  

F. Brain abscess and empyema

Brain Abscess

Symptoms and signs

  1. Headache
  2. Focal neurologic deficits
  3. Fever, chills and other signs of infection usually do not occur
  4. Papilledema (with increased ICP)
  5. Nausea, vomiting (with increased ICP)


  1. Focal neurologic deficit or seizure suggests focal brain lesion
  2. The patient may have a risk factor for abscess, such as:
  3. Contrast-enhanced CT or MRI may show a ring-enhancing lesion or lesions and surrounding brain edema
  4. If the diagnosis is in doubt, a stereotaxic brain biopsy will confirm that the lesion is an abscess

Cerebrospinal fluid

Lumbar puncture is not usually performed because abscess creates an intracranial mass with edema, so there is a risk of brain herniation. If the abscess is well-encapsulated, protein may be increased, but cell counts are usually low and cultures are usually negative, so the diagnostic usefulness of LP is limited even if the physician is bold enough to do it.


If the abscess is small and not causing severe neurologic deficit, presumptive antibiotic therapy can be given--usually a combination regimen that covers both aerobic and anaerobic organisms is needed. If the abscess grows or fails to resolve, then surgery will be needed for diagnosis and drainage.


Abscesses may arise by spread from an intracranial infection such as mastoiditis, but usually are spread to brain through the blood stream. Hematogenous spread from heart or lungs is most common. Congential heart disease with right to left shunting, pulmonary A-V fistulas, bronchiectasis, and lung abscess are all risk factors. Bacterial endocarditis is usually only a minor risk factor for brain abscess.
    Streptococcus viridans is the most commonly isolated organism, but abscesses are usually polymicrobial, and Staphylococcus aureus, hemolytic Streptococcus, Enterobacteriaciae, Bacteroides and other anaeobes, are also common. In immunocompromised patients, fungal or Toxoplasma gondii abscesses may occur.

Subdural empyema

Subdural empyema is a collection of pus in the subdural space, usually arising by direct spread from an intracranial infection such as sinusitis. Signs and symptoms are like those of brain abscess, but seizures are especially common, and treatment essentially always requires surgical drainage.

G. Myelitis and spinal epidural abscess


Symptoms are those of spinal cord dysfunction: weakness, sensory changes, bladder or bowel dysfunction. In the case of epidural abscess, localized back pain and fever are very common.


Signs are those of spinal cord dysfunction: paraparesis, sensory level, hyporeflexia or hyperreflexia with extensor plantar responses, loss of anal reflexes, loss of anal tone and loss of bulbocavernosus reflex.


  1. Characteristic signs and symptoms.
  2. MRI of the spine at the level suggested by the clinical exam.
  3. Lumbar puncture for suspected myelitis, but not for spinal epidural abscess.


Myelitis may occur along with meningeal or brain infection, but often occurs alone, causing a syndrome of acute transverse myelitis.  Acute transverse myelitis is characterized by the rapid onset of spinal cord dysfunction, without evidence for spinal cord compression or infarction. CSF pleocytosis occurs. It is usually thought to be of viral etiology.
    Spinal epidural abscess also produces a rapid-onset spinal cord syndrome. The most common cause is S. aureus. LP is contraindicated in spinal epidural abscess because: 1) by needling the abscess you may seed the CSF with bacteria, causing a meningitis, 2) you may precipitate spinal block, with immediate complete paraplegia.


Therapy for acute transverse myelitis is mainly just supportive, but treatment with high dose steroids is worth considering. Spinal epidural abscess is a medical emergency because loss of function can be prevented by prompt surgical drainage of the abscess, but if diagnosis or treatment is delayed until paraplegia occurs, recovery is very poor. Appropriate antibiotic therapy is essential.


Myelitis is usually caused by viral organisms. I usually treat it with steroids, but the results are usually unsatisfactory. Epidural abscess is uncommon, but not rare. It is a true medical emergency--if you diagnose the abscess, drain it, and treat with antibiotics before it causes severe spinal cord symptoms your patient will be able to walk out of the hospital. If you mistakenly believe it is something you can work up and treat at a leisurely pace, your patient will probably leave in a wheelchair.

H. A slide show of organisms causing meningitis

This is a "Rogues Gallery" of microscopic images of organisms that cause meningitis. Images are courtesy of Dr. Joan Barenfanger.

III. Lumbar puncture

Lumbar puncture is essential for diagnosis in most cases of meningitis and encephalitis (but not for abscess or empyema). The test is sensitive and specific for most organisms.

How to do it

Looking at the sample with the naked eye

Immediately upon obtaining the sample, it may be obvious that it is bloody or cloudy. In bacterial meningitis it is common to have thick cloudy fluid, usually implying a cell count in the thousands. In subarachnoid hemorrhage the fluid is frankly bloody, but it must be distinguished from merely a "traumatic tap". If the fluid becomes clear during the procedure, traumatic tap is likely.
    If the fluid looks normal with casual observation it could still be abnormal to the expert observer, who may detect xanthochromia. Xanthochromia is a yellowish or reddish discoloration of the spinal fluid caused by pigments resulting from breakdown of red blood cells. To test for it, the fluid should first be centrifuged to sediment out cells. In severe cases, the spun fluid may look like cherry "Kool-Aid". More subtle cases can be detected by holding the tube up to a window illuminated by sunlight. (Personally, I prefer the bright northern light of a cloudy winter day, but in a pinch a 5500 K halogen lamp will do.)  Observe the fluid for a yellowish tinge. If there are refractile particles, you didn't spin it long enough--these are WBCs or RBCs.

Looking at the sample with a microscope

Cell counts
Three pieces of equipment are required: a microscope, a hemocytometer, and coverslips of a weight appropriate for the hemocytometer. To do a cell count, place the coverslip on the hemocytometer, then place a drop of CSF in the well of the hemocytometer. The drop will be drawn under the coverslip by capillary action.
    The field of the hemocytometer will have nine subdivisions, and the central one will be further subdivided. The total volume under the slip is 0.9 cubic mm. If there are lots of cells, count the cells in one large square and multiply by 10 to get the total number of cells per cubic mm. If there are few cells, count all 9 squares. This technique will allow you to quickly obtain a count of total RBCs and WBCs, and will allow you to examine RBC morphology. If the RBCs are round, they are fresh, and likely are there because of a traumatic tap. If they are crenated (wrinkled), they are likely to have been in the CSF prior to the procedure.

Gram stain
For the truly devoted student of CSF, doing your own Gram stain is a must. For this, you will need, in addition to a microscope, a sink with running water, gloves, and the necessary staining paraphernalia. Instructions on this can be found elsewhere.

Tests to run on the sample

It is standard to obtain four tubes of CSF, each containing 1 or 2 cc of fluid. Standard tests include:
Tube #1: glucose and protein
Tube #2: cryptococcal antigen, Gram stain
Tube #3: bacterial cultures
Tube #4: cell count and differential

CSF glucose is normally 2/3 that of the serum. Hence, for an accurate assessment, a simultaneous serum glucose is necessary.  Glucose is normal in viral meningitis, and may be normal in chronic meningitis, but is often very low in acute bacterial meningitis.

Protein is increased in any condition in which a leaky blood brain barrier occurs. Hence, it is increased in conditions affecting the spinal nerve roots (diabetes, Guillian-Barre syndrome), may be increased in neoplasms of the CNS, or infections of the brain, spinal cord, or meninges. Protein may be markedly elevated in cases of spinal block (for example, severe cervical stenosis or neoplasm), but LP is contraindicated in patients with these conditions because of the risk of producing spinal cord compression. Protein is also increased with normal aging--a rule of thumb is that a person is "allowed" 1 mg/ml of protein per year of age.
    In case of traumatic tap, protein is increased because of the inclusion of cells and serum in the sample. A rule of thumb is that 1000 cells imply a 1 mg/ml increase in protein concentration. If accuracy is imperative, then the amount of protein to be expected can be calculated if the patient's serum protein concentration, RBC counts, and WBC counts are known.

WBC count
This is a critical number in cases of meningitis. The meninges are everywhere close to the spinal fluid spaces, and early in the course of illness, inflammatory cells spill from the meninges into the CSF. The WBC count is normally 5/cu. mm or less. It is increased into the tens and hundreds or thousands by septic meningitis.
    The differential can help in determining the type of infection. In aseptic meningitis, mononuclear forms, especially lymphocytes, predominate. In septic meningitis, polymorphonuclear forms predominate. If the overall count is normal the differential is not meaningful.
    A number of non-infectious conditions can produce small increases in CSF WBC counts, including:

RBC count
This is increased in subarachnoid hemorrhage and traumatic tap. The RBC morphology may be helpful--if they are crenated they are likely to have been present in the CSF for some time, and not caused merely by the trauma of the procedure (unless the specimen is allowed to sit on the desk of a ward clerk or a laboratory technician for a long time before it is examined).

Bacterial cultures
Cultures are the "gold standard" for diagnosis of bacterial meningitis. Normal CSF is always sterile, so if cultures grow the patient either has an infection, or the specimen was contaminated. In bacterial meningitis, cultures are positive in the large majority of cases: 80% for S. pneumoniae, 90% for N. meningitidis, 94% for H. influenzae. False-positive results occur if the culture is contaminated by skin organisms such as coagulase-negative staphylococcus, but this organism often is the infectious agent in cases of shunt infection. False-negative results are often obtained if the meningitis has been partially treated with antibiotics before the CSF specimen is obtained.
    It is worth noting that patients with meningitis are often also bacteremic, so blood cultures are usually positive as well.
    A drawback of CSF cultures is that it takes 24 to 48 hours for the organism to grow and be identified.

Gram stain
Gram stain is an essential part of the CSF examination whenever meningitis is considered. In addition to being practically 100% specific, it has a sensitivity of 60 to 80% for bacterial infection [13,14].

Bacterial antigen tests
Rapid bacterial antigen tests are available for S. pneumoniae, N. meningitidis, and H. influenzae.

Other tests
Other tests may be useful in particular clinical situations:

Typical CSF formulas

Bacterial Viral Fungal Tuberculous
opening pressure normal or high normal normal or high usually high
WBC count (cells/mm3) 1,000-10,000 < 300 20-500 50-500
PMN (%) >80 <20 <50 ~20
mononuclear forms 

RBC count (cells/mm3) slight increase normal normal normal
protein (mg/dl) very high (100-500) normal high high
glucose < 40 normal usually < 40 < 40
Gram stain  60-90 % positive negative negative AFB stain + in 40-80%
culture (% positive) 70-85 25 25-50 50-80

Relative contraindications to lumbar puncture

  1. Space-occupying intracranial lesions or obstructive hydrocephalus. The risk is that removing fluid from the lumbar space would exacerbate a pressure differential between intracranial compartments and lead to brain herniation. This is uncommon, but is a definite concern. Careful examination of the patient for signs of increased intracranial pressure (e.g. papilledema) is indicated. An emergency non-contrast CT scan of the head is also indicated. If a scan is not immediately available, your choice is between (a) presumptive treatment and no lumbar puncture, or (b) puncture without scan. Either may be the most reasonable depending on the clinical situation. Brain absess is thought to be especially likely to be associated with herniation. Papilledema and increased intracranial pressure are not by themselves a contraindication to LP. In fact, LP is a good therapy for the increased intracranial pressure of pseudotumor cerebri.
  2. Bleeding dyscrasia. If necessary, give two units of fresh frozen plasma and do the LP right away. But the risk of serious complication here is low, so do not delay long if you suspect bacterial meningitis--the two hours you delay may mean the difference between a normal life or a brain-damaged one.
  3. Spinal epidural abscess. Do not put a lumbar puncture needle through the abscess--you may seed the subarachnoid space with bacteria and cause a meningitis.

Possible complications

  1. Headache. Occurs in 20% of patients, caused by leakage of fluid through the hole made in the dura. Diagnosis is obvious--the headache is severe when standing but immediately goes away on lying down. Treatment is bedrest with the head lower than the hole, and drink plenty of fluids.
  2. Meningitis. Rare. Should occur only if there is some break in sterile technique--which is to say it should never occur.
  3. Contamination of the CSF sample. This is really bad form. Do not cough into your sample. You and the patient went to a lot of trouble--keep it sterile.
  4. Disk herniation? There are rare reports of disk herniation thought to be caused by a previous LP that punctured an intervertebral disk.
  5. Impalement of nerve roots. Not likely in a conscious patient, who will inform you quickly if he has lancinating pain shooting down one leg. It is more likely in an unconscious patient, so you may have to take the blame for it if the patient wakes up and finds he has a numb spot on his leg. But you may also get the credit for the patient waking up.
  6. Impalement of spinal cord. There is a popular misconception that paralysis is a possible complication of LP. This is not possible unless you do a thoracic or cervical puncture because the spinal cord ends at the L1/L2 disk. On the other hand, it is entirely possible if you do C1/C2 punctures, or err during thoracic epidural anesthesia.

IV. References

A good general review is:

Marra C.M. (editor), Central Nervous System Infections, Neurologic Clinics 14, Philadelphia, W.B. Saunders & Co. (1999).

Specific references are:

1 Schachat, A., Robinson, K., Wenger, J.D. and et al., Bacterial meningitis in the United States in 1995, N Engl J Med, 337 (1997) 970

 2 Progress toward eliminating Haemophilus influenzae type b disease among infants and children--United States, 1987-1997, MMWR, 47 (1998) 993

 3 Adams, W.G., Deaver, K.A., Cochi, S.L. and et al, Decline of childhood Haemophilus influenzae type b (Hib) disease in the Hib vaccine era, JAMA, 269 (1993) 221

 4 Murphy, T.V., White, K.E., Pastor, P. and et al., Declining incidence of Haemophilus influenzae type b disease since introduction of vaccination, JAMA, 269 (1993) 246

 5 Mylonakis, E., Hohman, E.L. and Calderwood, S.B., Central nervous system infection with Listeria monocytogenes: 33 years' experience at a general hospital and review of 776 episodes from the literature, Medicine (Baltimore), 77 (1998) 313

 6 Southwick, F.S. and Purich, D.L., Intracellular pathogenesis of listeriosis, N Engl J Med, 334 (1996) 770

 7 Gray, B.M., Converse, G.M.D. and Dillon, H.C.J., Epidemiologic studies of Streptococcus pneumoniae in infants, J Infect Dis, 142 (1980) 923

 8 Bishburg, E., Sunderam, G., Reichman, L.B. and et al., Central nervous system tuberculosis with the acquired immunodeficiency syndrome and its related complex, Ann Intern Med, 105 (1986) 210

 9 Cassleman, E.S., Hasso, A.N., Ashwal, S. and et al., Computed tomography of tuberculous meningitis in infants and children, J Comput Assist Tomogr, 4 (1980) 211

 10 Dooley, D.P., Carpenter, J.L. and Rademacher, S., Adjunctive corticosteroid therapy for tuberculosis: a critical reappraisal of the literature, Clin Infect Dis, 25 (1997) 872

 11 Fodor, P.A., Levin, M.J., Weinberg, A. and et al., Atypical herpes simplex virus encephalitis diagnosed by PCR amplification of viral DNA from CSF, Neurology, 51 (1998) 554

 12 Whitley, R.J., Kimberlin, D.W. and Roizman, B., Herpes simplex viruses, Clin Infect Dis, 26 (1998) 541

 13 Carpenter, R.R. and Petersdorf, R.G., The clinical spectrum of bacterial infection, Am J Med, 33 (1962) 262

 14 Dunbar, S.A., Eason, R.A., Musher, D.M. and et al., Microscopic examination and broth culture of cerebrospinal fluid in diagnosis of meningitis, J Clin Microbiol, 36 (1998) 1617

 15 Atkinson, P.J., Sharland, M. and Maguire, H., Predominant enteroviral serotypes causing meningitis, Arch Dis Child, 78 (1998) 373

 16 Gorgievski-Hrisoho, M., Schumacher, J.D., Vilimonovic, N. and et al., Detection by PCR of enterviruses in cerebrospinal fluid during a summer outbreak of aseptic meningitis in Switzerland, J Clin Microbiol, 36 (1998) 2408

 17 McIntyre, P.B., Berkey, C.S., King, S.M. and et al., Dexamethasone as adjunctive therapy in bacterial meningitis: a meta-analysis of randomized clinical trials since 1998, JAMA, 278 (1997) 925

18 Sampathkumar P., West Nile Virus: Epidemiology, Clinical Presentation, Diagnosis, and Prevention, Mayo Clin Proc, 78 (2003) 1137-1144

19 de Gans J., van de Beek D. for the European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators, Dexamethasone in adults with bacterial meningitis, N Engl J Med. 347 (2002) 1549-56.

20 Hanson R.A., Ghosh S., Gonzalez-Gomez I., Levy M.L., Gilles F.H. Abducens length and vulnerability? Neurology, 62 (2004) 33-36.

21 Kahn E.A., Cherry G.R. The clinical importance of spontaneous retinal venous pulsations. Univ Mich Med Bull 16 (1950) 305-398.

22 Cochlear implants may increase risk for bacterial meningitis. Public Health Rep 119 (2004) 97-98.

23 Cohen N, Ramos A, Ramsden R, Baumgarten W, Lesisnski A, O'donoghue G, Lenarz T, Fraysse B International consensus on meningitis and cochlear implants. Acta Otolaryngol 125 (2005) 916-917.

24 Yogev R, Guzman-Cottrill J Bacterial meningitis in children: critical review of current concepts.  Drugs 65 (2005) 1097-1112.

25 Goldwater PN Cefotaxime and ceftriaxone cerebrospinal fluid levels during treatment of bacterial meningitis in children. Int J Antimicrob Agents 26 (2005) 408-411.

26 Antal EA, Loberg EM, Dietrichs E, Maehlen J Neuropathological findings in 9 cases of listeria monocytogenes brain stem encephalitis. Brain Pathol 15 (2005) 187-191.

27 Harrison LH Prospects for vaccine prevention of meningococcal infection. Clin Microbiol Rev 19 (2006) 142-164.

28 Powers WJ Cerebrospinal fluid lymphocytosis in acute bacterial meningitis. Am J Med. 792 (1985) 16-20.

V. Quiz

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VI. Abbreviations

A-V, arteriovenous;
BP, blood pressure;
cc, cubic centimeters;
CN, cranial nerves;
CNS, central nervous system;
CSF, cerebrospinal fluid;
CT, computed tomography;
cu. mm, cubic millimeters;
DTR, deep tendon reflex;
ECG, electrocardiogram;
EEG, electroencephalography;
ENT, ear, nose and throat;
EOMI, extraocular movements intact;
GI, gastrointestinal;
HIV, human immunodeficiency virus;
HSV, herpes simplex virus;
ICP, intracranial pressure;
IV, intravenous;
LP, lumbar puncture;
mg, milligram;
ml, milliliter;
MMSE, mini-mental state examination;
MRI, magnetic resonance imaging;
OD, right eye;
OS, left eye;
P, pulse;
PCR, polymerase chain reaction;
PERRL, pupils equal, round, and reactive to light;
PO, by mouth;
R, respiration rate;
RBC, red blood cells;
SIADH, (syndrome of) serum inappropriate antidiuretic hormone;
sp., species;
T, temperature;
U.S., United States;
VDRL, venereal disease research laboratory (test for syphilis);
WBC, white blood cells
WMV, West Nile Virus.

VII. About this page

This essay contains information for 3rd and 4th year medical students (American system) rotating on the Neurology service at the Southern Illinois University School of Medicine. Address questions to the author.

Technical information

This page has been tested with Netscape 4.7 and Internet Explorer 5. A basic page will display with any browser, but for all features to be accessible, your browser must support cascading style sheets and Javascript must be enabled.

Revision history

1/21/2001, 4/22/2001, 11/20/2001, 5/16/2002, 7/11/2002, 9/23/2003, 3/24/2004, 2/7/2006, 1/13/2008

Copyright notice

Materials in this site are copyright 2001-8 by M. Steven Evans.


M. Steven Evans, M.D., M.S.
Associate Professor of Neurology and Microbiology/Immunology


Many thanks to Dr. Nancy Khardori, who kindly read this document and helped eliminate some errors.
Many thanks also to Dr. Joan Barenfanger, who supplied the excellent images of pathogenic organisms.
Any errors or inaccuracies that persist are strictly due to the author.


Department of Neurology
PO Box 19643
Southern Illinois University School of Medicine
Springfield, Illinois  62794-9643