Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 30-04: Infections of the Central Nervous System + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Central nervous system (CNS) infection is a medical emergency Immediate diagnostic steps must be instituted to establish the specific cause +++ General Considerations ++ Infections can be caused by almost any infectious agent, including Bacteria Mycobacteria Fungi Spirochetes Protozoa Helminths Viruses +++ ETIOLOGIC CLASSIFICATION ++ CNS infections can be divided into several categories that are readily distinguished by cerebrospinal fluid (CSF) examination as the first step toward diagnosis (Table 30–1) Purulent meningitis 18–50 years: Streptococcus pneumoniae, Neisseria meningitidis > 50 years: S pneumoniae, N meningitidis, Listeria monocytogenes, gram-negative bacilli Impaired cellular immunity: L monocytogenes, gram-negative bacilli, S pneumoniae Postsurgical or posttraumatic: Staphylococcus aureus, S pneumoniae, gram-negative bacilli Chronic meningitis Mycobacterium tuberculosis or atypical mycobacteria Fungi: Cryptococcus, Coccidioides, Histoplasma Spirochetes: Treponema pallidum, Borrelia burgdorferi Other: brucellosis, HIV infection Aseptic meningitis Mumps Herpes simplex virus, coxsackievirus, echoviruses Infectious mononucleosis Leptospirosis, syphilis, Lyme disease Drug-induced aseptic meningitis (eg, from nonsteroidal anti-inflammatory agents, sulfonamides and certain monoclonal antibodies) Encephalitis Partially treated bacterial meningitis Neighborhood reaction Noninfectious meningeal irritation Brain abscess Health care–associated meningitis May result from invasive neurosurgical procedures (eg, craniotomy, internal or external ventricular catheters, external lumbar catheters), complicated head trauma, or hospital-acquired bloodstream infections Outbreaks have been associated with contaminated epidural or paraspinal corticosteroid injections Microbiology is generally distinct from community-acquired meningitis, with the following playing a larger role: Gram-negative organisms (eg, Pseudomonas), S aureus, and coagulase-negative staphylococci Mold and fungi (Exserohilum rostratum and Aspergillus fumigatus) in outbreaks associated with contaminated corticosteroids ++Table Graphic Jump LocationTable 30–1.Typical cerebrospinal fluid findings in various central nervous system diseases.View Table||Download (.pdf) Table 30–1. Typical cerebrospinal fluid findings in various central nervous system diseases. Diagnosis Cells/mcL Glucose (mg/dL) Protein (mg/dL) Opening Pressure Normal 0–5 lymphocytes 45–851 15–45 70–180 mm H2O Purulent meningitis (bacterial)2 community-acquired 200–20,000 polymorphonuclear neutrophils Low (< 45) High (> 50) Markedly elevated Granulomatous meningitis (mycobacterial, fungal)3 100–1000, mostly lymphocytes3 Low (< 45) High (> 50) Moderately elevated Spirochetal meningitis 100–1000, mostly lymphocytes3 Normal High (> 50) Normal to slightly elevated Aseptic meningitis, viral meningitis, or meningoencephalitis4 25–2000, mostly lymphocytes3 Normal or low High (> 50) Slightly elevated “Neighborhood reaction”5 Variably increased Normal Normal or high Variable 1Cerebrospinal fluid glucose must be considered in relation to blood glucose level. Normally, cerebrospinal fluid glucose is 20–30 mg/dL lower than blood glucose, or 50–70% of the normal value of blood glucose.2Organisms in smear or culture of cerebrospinal fluid; counterimmunoelectrophoresis or latex agglutination may be diagnostic.3Polymorphonuclear neutrophils may predominate early.4Viral isolation from cerebrospinal fluid early; antibody titer rise in paired specimens of serum; polymerase chain reaction for herpesvirus.5May occur in mastoiditis, brain abscess, epidural abscess, sinusitis, septic thrombus, brain tumor. Cerebrospinal fluid culture results usually negative. + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Symptoms and signs common in all types of CNS infection Headache, fever Sensorial disturbances Neck and back stiffness Positive Kernig and Brudzinski signs CSF abnormalities Although it is rare for all of these manifestations to be present in any one individual, the presence of even one should suggest the possibility of a CNS infection The classic triad of fever, stiff neck and altered mentation has low sensitivity for bacterial meningitis (44%) However, nearly all patients with bacterial meningitis have at least two of the following symptoms: fever, headache, stiff neck, or altered mental status +++ Differential Diagnosis ++ Subarachnoid hemorrhage Encephalitis "Neighborhood reaction" causing abnormal CSF, such as Brain abscess Epidural abscess Vertebral osteomyelitis Mastoiditis Sinusitis Brain tumor Dural sinus thrombosis Noninfectious meningeal irritation Carcinomatous meningitis Sarcoidosis Systemic lupus erythematosus Drugs (eg, nonsteroidal anti-inflammatory drugs, trimethoprim-sulfamethoxazole) Pneumonia Shigellosis If fever and rash Gonococcemia Infective endocarditis Thrombotic thrombocytopenic purpura Rocky Mountain spotted fever Viral exanthem Seizure due to other cause eg, febrile seizure + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ See Table 30–1 Complete blood count, blood culture Lumbar puncture followed by careful study and culture of the CSF Fluid must be examined for cell count, glucose, and protein, and a smear stained for bacteria (and acid-fast organisms when appropriate) and cultured for pyogenic organisms and for mycobacteria and fungi when indicated Latex agglutination tests can detect antigens of encapsulated organisms (S pneumoniae, Haemophilus influenzae, N meningitidis, and Cryptococcus neoformans) but are rarely used except for detection of Cryptococcus or in partially treated patients Polymerase chain reaction (PCR) for herpes simplex, varicella-zoster, and JC virus is very sensitive (> 95%) and specific PCR to detect other organisms may not be any more sensitive than culture (or serology), but the real value is the rapidity with which results are available, ie, hours compared with days or weeks +++ Imaging Studies ++ Chest radiograph Obtain CT scan In immunocompromised patients and those with moderate to severe impairment of mental status Before lumbar puncture if a space-occupying lesion is suspected on the basis of papilledema, coma, seizures, or focal neurologic findings (Performing a lumbar puncture in the presence of a space-occupying lesion [brain abscess, brain cancer, subdural hematoma, subdural abscess, necrotic temporal lobe from herpes encephalitis] may result in brainstem herniation) MRI with contrast of the epidural injection site and surrounding areas Recommended (sometimes repeatedly) following a possibly contaminated corticosteroid injection for patients with symptoms Used to exclude epidural abscess, phlegmon, vertebral osteomyelitis, discitis, or arachnoiditis + Treatment Download Section PDF Listen +++ +++ Medications ++ Avoid delay in treatment: if CT scan is delayed and bacterial meningitis is suspected, draw blood cultures and administer antibiotics and corticosteroids even before CSF is obtained (Table 30–2) Antibiotics given within 4 hours before obtaining CSF probably do not affect culture results Increased intracranial pressure due to brain edema often requires treatment with hyperventilation, mannitol (25–50 g bolus intravenous infusion), dexamethasone (4 mg intravenously every 4–6 hours) Empiric antifungal therapy with voriconazole, in addition to routine empiric treatment for other pathogens, is recommended until the specific cause of the patient's CNS or parameningeal infection has been identified ++Table Graphic Jump LocationTable 30–2.Initial antimicrobial therapy for purulent meningitis of unknown cause.View Table||Download (.pdf) Table 30–2. Initial antimicrobial therapy for purulent meningitis of unknown cause. Population Usual Microorganisms Standard Therapy 18–50 years Streptococcus pneumoniae, Neisseria meningitidis Vancomycin1 plus ceftriaxone2 Over 50 years S pneumoniae, N meningitidis, Listeria monocytogenes, gram-negative bacilli, group B streptococcus Vancomycin1 plus ampicillin,3 plus ceftriaxone2 Impaired cellular immunity L monocytogenes, gram-negative bacilli, S pneumoniae Vancomycin1 plus ampicillin3 plus cefepime4 Postsurgical or posttraumatic Staphylococcus aureus, S pneumoniae, aerobic gram-negative bacilli, coagulase-negative staphylococci,5 diphtheroids (eg, Propionibacterium acnes)5 (uncommon) Vancomycin1 plus cefepime4 1Given to cover highly penicillin- or cephalosporin-resistant pneumococci. The dose of vancomycin is 15 mg/kg/dose intravenously every 8 hours. Vancomycin trough levels should be maintained at > 15 mcg/mL. Stopped if the causative organism is susceptible to ceftriaxone.2Ceftriaxone can often be used safely in most patients with a history of penicillin allergy (aztreonam can be considered for empiric coverage of gram-negative bacilli in patients with Type 1 IgE-mediated penicillin and cephalosporin allergy). The usual dose of ceftriaxone is 2 g intravenously every 12 hours. If the organism is susceptible to penicillin, 3–4 million units intravenously every 4 hours is given.3In severely ill patients, ampicillin is used when L monocytogenes infection is a consideration. For confirmed infection due to L monocytogenes, gentamicin is sometimes added to ampicillin. (For patients with Type 1 IgE-mediated penicillin allergy, trimethoprim-sulfamethoxazole [TMP-SMZ] in a dosage of 15–20 mg/kg/day of TMP in 3 or 4 divided doses can be considered.) The dose of ampicillin is usually 2 g intravenously every 4 hours.4Cefepime is given in a dose of 3 g intravenously every 8 hours.5Primarily associated with presence of hardware. +++ PURULENT MENINGITIS ++ Treat presumptive microorganism based on age group (Table 30–2) The identity of the causative microorganism may remain unknown for a few days Duration of therapy for bacterial meningitis H influenzae, 7 days N meningitidis, 3–7 days S pneumoniae, 10–14 days L monocytogenes, 14–21 days Gram-negative bacilli, 21 days For pneumococcal meningitis: give dexamethasone 10 mg intravenously 15–20 min before or simultaneously with the first dose of antibiotics and continue every 6 hours for 4 days +++ BRAIN ABSCESS ++ Drainage and 3–4 weeks of systemic antibiotics directed against organisms isolated Frequent regimen: metronidazole, 500 mg intravenously or orally every 8 hours, plus ceftriaxone, 2 g every 12 hours with or without vancomycin, 10–15 mg/kg/dose intravenously every 12 hours; vancomycin trough serum levels should be >15 mcg/mL In cases where abscesses are < 2 cm in size, where there are multiple abscesses that cannot be drained, or if an abscess is located in an area where significant neurologic sequelae would result from drainage, antibiotics can be used for 6–8 weeks without drainage +++ THERAPY OF OTHER TYPES OF MENINGITIS ++ See specific diagnoses +++ Surgery ++ Brain abscesses need drainage (excision or aspiration) if ≥ 4 cm in size, plus systemic antibiotics +++ Therapeutic Procedures ++ Treatment of cerebral edema and increased intracranial pressure may require drainage of CSF by repeated lumbar puncture and placement of ventricular catheters + Outcome Download Section PDF Listen +++ +++ Follow-Up ++ Monitor CNS pressures if extraventricular drain is in place +++ Prognosis ++ Prompt antibiotic therapy probably improves outcome in bacterial meningitis Dexamethasone therapy for pneumococcal meningitis decreases morbidity and mortality +++ Prevention +++ PNEUMOCOCCAL VACCINE ++ Recommended for patients with Asplenia Sickle cell disease Chronic illnesses (eg, cardiopulmonary disease, alcoholism, cirrhosis, chronic kidney disease, nephrotic syndrome, CSF leaks) Asthma Immunocompromise (eg, patients with Hodgkin disease, lymphoma, chronic lymphocytic leukemia, plasma cell myeloma [formerly multiple myeloma], congenital immunodeficiency, asymptomatic or symptomatic HIV infection, organ or bone marrow transplant recipients) Patients who receive immunosuppressive therapy, who smoke cigarettes, or who are Alaskan Natives should also receive the vaccine Because of the apparent increased risk of developing pneumococcal meningitis following cochlear implants, patients receiving these implants should be vaccinated +++ MENINGOCOCCAL VACCINE ++ Should be administered to asplenic patients or those with terminal complement deficiencies A new conjugated polysaccharide vaccine is now recommended as a routine vaccination for preadolescents aged 11–12 and as "catch-up" vaccination for previously unvaccinated teens entering high school or college (Table 30–7) Other groups recommended for vaccination include College freshman living in dormitories (the risk to nonfreshman and freshman not living in dormitories is the same as the general population and vaccination of these groups is elective) Microbiologists who are routinely exposed to N meningitidis Military recruits Persons who travel to or reside in areas in which N meningitidis is hyperendemic or epidemic ++Table Graphic Jump LocationTable 30–7.Recommended adult immunization schedule—United States, 2020.View Table||Download (.pdf) Table 30–7. Recommended adult immunization schedule—United States, 2020. +++ When to Refer ++ Patients with acute meningitis Immunosuppressed patients Patients with chronic meningitis All patients with brain abscesses and encephalitis Patients with suspected hospital-acquired meningitis (eg, those who have undergone recent neurosurgery or epidural or paraspinal corticosteroid injection) Patients with recurrent meningitis +++ When to Admit ++ Patients with suspected acute meningitis, encephalitis, and brain or paraspinous abscess There is less urgency to admit patients with chronic meningitis, but these patients may be admitted to expedite diagnostic procedures and coordinate care, particularly if no diagnosis has been made in the outpatient setting + References Download Section PDF Listen +++ + +Federspiel F et al. Eosinophilic meningitis due to Angiostrongylus cantonensis in Europe. Int J Infect Dis. 2020 Apr;93:28–39. [PubMed: 31972289] + +Fitzgerald D et al. Invasive pneumococcal and meningococcal disease. Infect Dis Clin North Am. 2019 Dec;33(4):1125–41. [PubMed: 31668194] + +Jarvis JN et al. Short-course high-dose liposomal amphotericin b for human immunodeficiency virus-associated cryptococcal meningitis: a phase 2 randomized controlled trial. Clin Infect Dis. 2019 Jan 18;68(3):393–401. [PubMed: 29945252] + +Lindsey NP et al. Notes from the field: multistate outbreak of eastern equine encephalitis virus—United States, 2019. MMWR Morb Mortal Wkly Rep. 2020 Jan 17;69(2):50–1. [PubMed: 31945032] + +McKay SL et al. Increase in acute flaccid myelitis—United States, 2018. MMWR Morb Mortal Wkly Rep. 2018 Nov 16;67(45):1273–5. [PubMed: 30439867] + +Morens DM et al. Eastern equine encephalitis virus—another emergent arbovirus in the United States. N Engl J Med. 2019 Nov 21;381(21):1989–92. [PubMed: 31747726] + +Tunkel AR et al. 2017 Infectious Diseases Society of America's clinical practice guidelines for healthcare-associated ventriculitis and meningitis. Clin Infect Dis. 2017 Mar 15;64(6):e34–65. [PubMed: 28203777] + +Wilson MR et al. Clinical metagenomic sequencing for diagnosis of meningitis and encephalitis. N Engl J Med. 2019 Jun 13;380(24):2327–40. [PubMed: 31189036]