• The central nervous system (CNS) is encased within three membranous layers, called meninges. These meninges, from the outermost layer inward, are the dura mater, the arachnoid, and the pia mater. The dura adheres to the inner surface of the cranium;
the arachnoid attaches to the inner surface of the dura; and the pia is attached to the brain, following all of its contours. The space between the arachnoid and pia—the subarachnoid space—is filled with cerebrospinal fluid (CSF).
• The cranial dura extends through the foramen magnum to become the spinal dura mater. The spinal epidural space is located between the periosteum of the vertebrae and the dura and is filled with fatty connective tissue and a vertebral venous plexus.
• The spinal arachnoid closely attaches to the inner surface of the dura, creating the sub-arachnoid space between itself and the spinal cord that, like the cranial subsub-arachnoid space, is filled with CSF. The spinal cord ends (i.e., becomes the cauda equina) at about the level of the disk between the first and second lumbar vertebrae; however, the spinal dural sheath (and its arachnoid lining) ends at about the second sacral vertebra. The large subarchnoid cistern, between these two points, is the site at which sampling of CSF occurs (i.e., lumbar puncture) with relatively little risk of damage to the spinal cord.
Scope of the Problem
• Meningitis
• Meningitis is inflammation of the membranes of the brain or spinal cord, which may accompany an infectious, neoplastic, toxic, or autoimmune process. Because the precise etiology may not be evident in the emergency department, empiric treat-ment for bacterial meningitis is of utmost importance.
• Despite early and aggressive use of antibiotics, the overall mortality rate remains at 25% for bacterial and fungal meningitis.
• The causative organism varies with the age, immune status, living conditions, travel history, and overall health of the individual. However, with the decline in frequency of Haemophilus influenzae meningitis as a result of the H. influenzae type b vaccine, S.
pneumoniae is now the most common cause in adults and children over one month old. N. meningitidis is the second most common organism isolated in both age groups.
• Antibiotic resistance is a frequently observed trend, with increasing resistance of S.
pneumoniae to penicillin and third-generation cephalosporins.
• Long-term sequelae of bacterial meningitis include cognitive deficits, seizure disorders, hearing loss, blindness, gait disturbances, focal motor deficits, and hydrocephalus.
• “Aseptic” meningitis refers to conditions in which there is CSF pleocytosis and a clinical suspicion of meningitis, but with negative bacterial cultures. Typical etiolo-gies include viral meningitis, fungal infections, and drugs (e.g., NSAIDs, TMP-SMX, and INH).
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• Encephalitis
• Encephalitis is inflammation of the brain parenchyma. It may coexist with viral meningitis or it may present as a distinct entity, caused most commonly by arbovi-ruses, herpes viarbovi-ruses, and rabies. Listeria and cat-scratch disease are rare etiologies.
• Encephalitides caused by certain arboviruses (Japanese, Eastern equine, and St. Louis encephalitides) are associated with high mortality rates and severe neurologic sequelae.
The death rate from HSV encephalitis has been reduced by acyclovir; however neuro-logic deficits—including epilepsy, focal motor deficits, and altered mentation—are com-mon.
• West Nile Virus
• West Nile virus, an arthropod-borne virus (arbovirus), may cause encephalitis, men-ingitis, or meningoencephalitis. Patients at highest risk for symptomatic infection include persons over age 50 and the immunosuppressed. Associated symptoms may include fever, headache, nausea, vomiting, weakness, altered mental status, stiff neck, and an erythematous rash. West Nile virus is not cultured from the CSF or brain tissue, but IgM antibodies may be present in the CSF or serum. Alternatively, PCR testing of the CSF for West Nile virus RNA may be positive.
• CNS Abscess
• CNS abscess denotes a circumscribed collection of purulent material, or a localized in-fection, which may exist within the brain parenchyma (brain abscess); within the meninges (epidural or subdural empyema); or within or surrounding the spinal cord (intramedul-lary or epidural spinal abscess). Complications of intracranial abscess include epilepsy, focal motor or sensory deficits, and intellectual deficits. Patients with spinal abscesses may have residual motor or sensory deficits, or bowel or bladder dysfunction.
Risk Factors
• Meningitis
• As mentioned above, the most common pathogens in patients over one month of age are S. pneumoniae and N. meningitidis; risk factors for other organisms are shown in Table 4D.1.
• Encephalitis
• The means of access to the CNS varies according to the virus (Table 4D.2).
• CNS Abscess
• CNS abscesses develop as an extension of a contiguous infection (e.g., otitis media, sinusitis, dental infection), or by hematogenous seeding from a remote site (e.g., pulmonary, endocarditis, osteomyelitis). Other risk factors include intravenous drug abuse, neurosurgical procedures, and penetrating head injury. The causative organ-isms vary according to the primary source of the infection and the immune status of the patient (Table 4D.3).
Diagnosis
History• The classic triad of fever, nuchal rigidity, and altered mental status is seen in ap-proximately two-thirds of patients with community-acquired bacterial meningitis.
All patients, however, will likely have at least one of these findings. Other signs and symptoms which should cause one to suspect meningitis include headache, chills, vomiting, myalgias/arthralgias, lethargy, malaise, focal neurologic deficits, photo-phobia, and seizures. Elderly patients may present with subtle findings, frequently limited to an altered sensorium. Fungal meningitides present with an atypical constellation of symptoms, including headache, low-grade fever, weight loss, and fatigue; similarly, tuberculous meningitis may be associated with fever, weight loss, night sweats, and malaise, with or without headache and meningismus.
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• Other important historical factors include:
• Duration of symptoms: a fulminant course indicates a bacterial meningitis or ag-gressive viral encephalitis, while a subacute presentation suggests a viral, fungal, or parasitic infection.
Table 4D.1. Organisms causing meningitis
Population Additional Potential Pathogens
Neonate (<1 mo) Group B streptococci, E. coli, Listeria monocytogenes 1 mo to 50 yr H. influenzae (rarely), L. monocytogenes (unlikely) Adults (over 50 yr), alcoholics, L. monocytogenes, Enterobacteriaceae
other debilitating diseases
Closed head injury with CSF leak S. aureus, Enterobacteriaceae, P. aeruginosa Recent neurosurgical procedure S. aureus, S. epidermidis, other Streptococcus or penetrating head injury species, Bacteroides fragilis, Enterobacteriaceae CSF shunt infection S. epidermidis, S. aureus, Enterobacteriaceae,
diphtheroids, P. acnes
Splenectomy H. influenzae
Chronic otitis media Streptococcus species, Enterobacteriaceae Bacteroides fragilis
Malignant otitis externa (diabetes) Pseudomonas species Sickle-cell disease, diabetics Enterobacteriaceae
Immunosuppressed host L. monocytogenes, P. aeruginosa, Enterobac teriaceae, S. aureus, H. influenzae, Streptococci, anaerobes, Mycobacterium tuberculosis, Actinobacter spp., syphilis, Cryptococcus neoformans, toxoplasmosis, Herpes simplex, Cytomegalovirus
Table 4D.2. Encephalitis, causative organisms
Virus Route of Entry
Arbovirus Mosquito bite; hematogenous spread
(California, W. Equine, E. Equine, St. Louis, West Nile)
Herpes virus
Herpes simplex type 1 Skin lesions; retrograde neuronal spread Varicella zoster Skin lesions; retrograde neuronal spread
E-B virus Mononucleosis
Rabies Animal bite; retrograde neuronal spread
Measles, mumps Post-infectious
Table 4D.3. Etiology of CNS abscess
Source of Infection Likely Pathogen
Local or remote infection
Sinuses, teeth Streptococci
Otitis media, pulmonary infection Bacteroides
Endocarditis S. aureus
Other sources Enterobacteriaceae, Nocardia (rarely) Neurosurgical procedure, S. aureus, Enterobacteriaceae penetrating head injury
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• Antecedent infection: recent otitis media, sinusitis, respiratory tract infection, phar-yngitis, or intracranial abscess may suggest recent colonization with, or contiguous spread of, a particular organism.
• Recent course of antibiotics: may alter CSF analysis and clinical presentation.
• History of a penetrating or closed head injury, neurosurgical procedure (including VP shunt placement), or congenital dural defect.
• Living conditions or epidemic exposure: college dormitories, military barracks, and jails/prisons are typical areas for epidemics of N. meningitidis; exposure in day-care centers, or to family members with a specific infectious disease (e.g., M. tuberculosis) may suggest an otherwise atypical causative organism.
• Immune suppression: HIV, malignancy, splenectomy, or other immunologic deficits.
• Social history: alcohol or IV drug abuse, low socioeconomic status.
• Underlying medical conditions: sickle cell disease or thalassemia major, bacterial endocarditis, cirrhosis, diabetes.
• Barrier disruption: VP shunt, central IV lines, loss of cutaneous integrity (includ-ing prior varicella-zoster infection).
• History of mosquito or tick bite; exposure to animals at risk for rabies infection.
Examination
• Meningitis
• Evaluate the patient’s overall appearance and mental status.
• HEENT exam should include a search for evidence of trauma, surgery, infections (otitis, mastoiditis, sinusitis, pharyngitis), or pupillary abnormalities. Note that papilledema takes time to develop, and this finding can be absent in the majority of patients with bacterial meningitis. In infants <12 mo of age, when meningeal signs are unreliable, the anterior fontanelle should be evaluated for bulging.
• Test the neck for rigidity: Brudzinski’s sign (if the neck is passively flexed, flexion of the hips occurs; or, on passive flexion of one hip, flexion of the other hip occurs);
and Kernig’s sign (resistance to passive extension of the knee). Neck stiffness is often absent at the extremes of age, or in patients with altered levels of conscious-ness, immunosuppressed, or partially treated disease.
• Examination of the chest may reveal a concurrent pneumonia.
• A new heart murmur may indicate endocarditis.
• Examination of the abdomen may suggest an infectious process, and thus a source for bacteremia and meningitis or abscess.
• A complete neurologic exam must be documented, revealing a number of potential abnormalities: isolated cranial nerve deficits (including ophthalmoplegia); focal mo-tor or sensory deficits; cerebellar dysfunction; and increased deep tendon reflexes.
Localizing signs are generally absent in bacterial meningitis; their presence suggests the possibility of a focal infection, such as an abscess. The level of consciousness may range from confusion or delirium to stupor or coma.
• The skin should be examined for the petechial or hemorrhagic lesions suggestive of meningococcemia, or a rash characteristic of HSV, herpes zoster, or leptospirosis (pur-pura and petechiae on the oral, vaginal, or conjunctival mucosa).
• Arthritis may be associated with N. meningitidis or, less commonly, other bacterial meningitides.
• Encephalitis
• Clinical suspicion of encephalitis should be raised in the setting of new “psychiatric”
symptoms, cognitive deficits (especially memory disturbances and aphasia), acute con-fusion, and movement disorders (e.g., choreoathetosis and parkinsonism).
• Abscess
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• Patients with CNS abscess often experience a delay in diagnosis as a result of non-specific presenting complaints.
• While headache is almost universally present, fever is seen approximately half of the time.
• One-third of patients may have focal neurologic signs, including hemiparesis and seizures.
• Increased intracranial pressure may cause vomiting, confusion, or altered levels of consciousness in 50% of patients.
• Meningismus is noted on <50% of exams, while papilledema is present in one-third of patients.
Evaluation
• Delay in the diagnosis of bacterial meningitis in the elderly, especially with nonspecific symptoms, is responsible for the high mortality in this population. While urinalysis or chest X-ray may indicate an infectious process outside the CNS, it is important to re-member that the diagnosis of meningitis still needs to be suspected—and aggressively pursued—because of the risk of hematogenous spread of the involved organisms.
Laboratory
• Cerebrospinal Fluid
• Lumbar puncture (LP) should be performed whenever meningitis is suspected. If there will be a delay in performing the LP, blood cultures should be drawn and antibiotics administered empirically. Immediate LP may be contraindicated in the following situations:
• Suspected HIV disease
• Focal neurologic exam
• Evidence of increased intracranial pressure
• Hemodynamic instability
• Overlying infection at the LP site
• Suspected coagulopathy
• Suspect subarachnoid hemorrhage
• An opening pressure, if measured, should be performed with the patient fully extended.
Normal adult pressures are 5-19 cm H2O, when the patient is in the lateral recumbent position. Opening pressure may be elevated in bacterial and fungal meningitis.
• The cerebrospinal fluid is normally clear and colorless. Infection, inflammation, or bleeding may cause the fluid to be turbid. Note that fluid can be clear even when several hundred cells are present.
• True CNS bleeding (e.g., a subarachnoid hemorrhage) may be distinguished from a traumatic tap by the presence of xanthochromia. In addition, RBC count will gen-erally decrease in sequential tubes with a traumatic tap.
• CSF analysis should include cell count and differential, glucose and protein, stat gram’s stain and culture, and a fourth tube for special tests as indicated by the clinical scenario.
• Normal adult CSF contains <6 WBCs/mm3, with no more than one PMN. Early in the course of bacterial meningitis, lymphocytes may predominate.
• CSF analysis in viral meningitis and encephalitis typically reveals <500 WBCs/
mm3, with almost 100% mononuclear cells (but early presentations may have PMN pleocytosis).
• Brain abscess and parameningeal infections (e.g., subdural empyema, epidural abscess) have cell counts and differentials similar to those of viral meningitis.
• The normal ratio of CSF:serum glucose is 0.6 (0-0.4 in the setting of severe hyperg-lycemia). CSF glucose may be decreased in bacterial, fungal and tuberculous
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meningitis; carcinomatous meningitis, and (normal or decreased) in subarachnoid hemorrhage. Mild decreases in CSF glucose may be seen in viral and parameningeal processes.
• CSF protein levels are normally <45 mg/dl in adults. An elevated protein, usually
>150 mg/dl, is suggestive of bacterial meningitis. Other causes of elevated CSF pro-tein include any infectious meningitis, viral or parasitic encephalitis, carcinomatous meningitis, subarachnoid hemorrhage, CNS vasculitis, neurosyphilis, hepatic encepha-lopathy, and demyelination syndromes.
• Other tests to consider include viral cultures, acid-fast stain and culture for M. tuber-culosis, India ink and cryptococcal antigen, VDRL, cytology, bacterial antigens for S.
pneumoniae, H. influenzae, and N. meningitidis (especially in patients recently treated with antibiotics), and Borrelia antibodies in cases of suspected Lyme disease. Other more specialized tests are rarely ordered in the ED.
• Blood Tests
• Although a CBC with differential may add to the clinical picture in a patient with suspected meningitis, a normal result does not exclude the diagnosis.
• PT and PTT may be useful to exclude a suspected coagulopathy, or DIC.
• Serum electrolytes, BUN/Cr, and glucose are routinely ordered.
• Blood cultures (two specimens, collected 15 min apart) may identify the organism in up to 80% of cases depending upon the etiology.
• Imaging
• A CT scan of the head should be performed prior to LP in the following situations:
• Altered mental status
• Focal neurologic exam (excluding ophthalmoplegia)
• Evidence of increased intracranial pressure
• Minimal or absent fever
• Recent-onset seizure
• Suspected subarachnoid hemorrhage or intracranial mass lesions
• Contrast-enhanced CT is the study of choice for evaluation of possible CNS ab-scess. Although not readily available, MRI is equally sensitive.
• MRI is the imaging study of choice when cranial epidural abscess or subdural em-pyema is suspected.
• A chest X-ray may reveal a concomitant pneumonia, especially in cases of pneumo-coccal meningitis.
• EEG
• In the setting of suspected herpes encephalitis, focal or lateralized EEG abnormali-ties may help pinpoint the diagnosis.
Treatment
• Meningitis
• Administration of IV antibiotics should begin as soon as the suspicion of bacterial meningitis is entertained. Empiric therapy should be based on the suspected patho-gen, taking into consideration the patient’s age and risk factors for specific organ-isms. An infectious disease consultant may be helpful for information regarding local drug resistance patterns (Table 4D.4).
• Encephalitis
• Herpes simplex and varicella encephalitis are the only treatable forms of encephali-tis. Acyclovir is dosed at 10mg/kg IV q8 h.
• CNS Abscess
• The mainstay of treatment of CNS abscess is antibiotics. Neurosurgical consulta-tion is recommended for possible aspiraconsulta-tion or excision (Table 4D.5).
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• Specific Treatment
• Meningitis
• Glucocorticoids, based on studies in children with predominantly H. influenzae type b meningitis, have been shown to reduce the morbidity associated with an inflammatory reaction to bacteriolysis. Dexamethasone, 0.15 mg/kg IV, may be considered in children as well as adults, especially in cases with positive Gram’s stain (indicating a high bacterial load), altered level of consciousness, or increased intracranial pressure. If dexamethasone is given, benefit is greatest when started prior to or concurrent with initial antibiotic therapy.
• In areas with high prevalence of drug-resistant S. pneumoniae, vancomycin is added empirically.
• In penicillin-allergic patients, trimethoprim-sulfamethoxazole and vancomycin are recommended.
• Amphotericin B and flucytosine are the drugs of choice for cryptococcal men-ingitis.
• Initial therapy for tuberculous meningitis should include isoniazid (INH), rifampin, ethambutol, and pyrazinamide (PZA).
Table 4D.4. Empiric antimicrobial therapy for meningitis
Population Empiric Therapy
Neonate (0-7 days) Ampicillin + Cefotaxime or Ampicillin + Gentamicin or Ampicillin + Amikacin Neonate (8-28 days) Ampicillin + Cefotaxime
1 mo to 50 yr Vancomycin + Ceftriaxone or
Vancomycin + Cefotaxime
Adults (over 50 yr) Ampicillin + Ceftriaxone + Vancomycin or Ampicillin + Cefotaxime + Vancomycin Recent neurosurgical procedure, Vancomycin + Ceftazidime
penetrating head injury, CSF leak
CSF shunt infection Peds: Vancomycin + Cefotaxime or Vancomycin + Ceftriaxone Adults: Vancomycin + Rifampin Immunosuppressed host Ampicillin + Ceftazidime +Vancomycin Suspected HSV 2 meningitis Acyclovir
Table 4D.5. Antibiotic therapy of CNS abscess
Source Empiric Therapy
Otogenic Ceftriaxone + metronidazole or
Cefotaxime + metronidazole Sinogenic, odontogenic Penicillin G + metronidazole Remote infection Penicillin G + metronidazole
Post-surgical, head trauma (Cefotaxime or Ceftriaxone) + nafcillin or (Cefotaxime or Cefotaxime) + oxacillin or (Cefotaxime or Ceftriaxone) + vancomycin (MRSA) Unknown source Ceftriaxone + metronidazole or
Cefotaxime + metronidazole
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• If the CSF pressure is >40 cm H2O, consider giving mannitol. Only the CSF in the manometer should be collected, to reduce the risk of tentorial herniation.
Patients with clinical and CT evidence of increased intracranial pressure also require appropriate therapy.
• Complications of meningitis should be anticipated and managed including de-hydration, hypotensive shock, hyponatremia, coagulopathies, seizures, cerebral edema, loss of protective airway reflexes, respiratory failure, and stroke.
• Close contacts of patients diagnosed with H. influenzae type b or N. meningitidis should receive prophylactic treatment. Health care personnel coming into con-tact with respiratory droplets are also candidates for prophylaxis (Table 4D.6).
• Encephalitis
• Post-infectious encephalomyelitis—an acute inflammatory, demyelinating pro-cess preceded by infection or immunization with influenza, measles, and vari-cella—is treated with high-dose intravenous methylprednisolone.
• Bacterial causes of encephalitis include Listeria, Lyme disease, Rocky Moun-tain Spotted Fever (RMSF), Leptospirosis, and the Ehrlichioses.
• Immunocompromised patients are at increased risk for amebic encephalitis, toxo-plasmosis, and CMV, in addition to the herpes viruses. Empiric therapy of en-cephalitis—in addition to acyclovir—is shown in Table 4D.7.
• CNS abscess
• Although not a true abscess, focal lesions in the brain parenchyma attribut-able to toxoplasmosis in the immunocompromised patient are treated with pyrimethamine plus sulfadiazine. Patients with sulfa allergies are treated with pyrimethamine plus clindamycin. If a fungal abscess is suspected, ampho-tericin B should be added to the empiric regimen.
• Treatment of epidural abscess and subdural empyema includes surgical drainage and intravenous antibiotics, as described above for empiric therapy of CNS abscess.
Table 4D.6. Meningitis prophylaxis
Organism Treatment
H. influenzae type b: Rifampin, 20 mg/kg PO (up to 600 mg) q 12 h for 4 doses N. meningitidis: Peds: Rifampin 10 mg/kg PO q 12 h for 4 doses or
Ceftriaxone 125 mg IM, single dose Adults: Rifampin 600 mg PO q 12 h for 4 doses or
Azithromycin 500 mg PO, single dose Ciprofloxacin 500 mg PO, single dose or Ceftriaxone 250 mg IM, single dose
Table 4D.7. Encephalitis, empiric therapy
Organism Treatment
Lyme disease Ceftriaxone
RMSF Peds <8 yo: Chloramphenicol
Adults: Doxycycline
Leptospirosis Penicillin G
Ehrlichiosis Doxycycline
Amebae Amphotericin
CMV Gancylcovir or foscarnet (more toxicity)
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Disposition
• All patients with suspected bacterial meningitis, encephalitis, or CNS abscess are ad-mitted.
• Patients definitively diagnosed with viral meningitis, if the social situation permits, may be discharged if associated symptoms (e.g., pain, vomiting) are controlled.
Suggested Reading
1. Disorders of consciousness approach to diagnosis and acute confusional states. In: Simon RP, Aminoff MJ, Greenberg DA, eds. Clinical Neurology 4th ed. Stamford, Appleton and Lange, 1999.
2. Gilbert DN, Moellering RC, Sande MA, eds. The Sanford Guide to Antimicrobial Therapy. 32nd ed. Hyde Park: Antimicrobial Therapy Inc., 2002.
3. Lavoie FW. Meningitis, Encephalitis, and Central Nervous System Abscess. In: Rosen P, Barkin RM, eds. Emergency Medicine: Concepts and Clinical Practice. 4th ed. St. Louis:
Mosby Year Book Inc., 1996.
4. Pruitt AA. Infections of the Nervous System. Neurol Clin North Am 1998; 16:2