Definition
A.Inflammation of the meninges, the three membranes surrounding the brain and spinal cord.
B.Types of meningitis.
1.Bacterial meningitis: Acute infection of the meninges and cerebrospinal fluid (CSF), characterized by an elevated number of white blood cells and positive bacterial cultures in the CSF. This type of meningitis has the highest rate of morbidity and mortality of all forms of disease.
2.Viral meningitis: Acute viral infection of the meninges and CSF, characterized by a moderate elevation of white blood cells in the CSF with negative bacterial cultures. Often referred to as aseptic meningitis due to lack of growth in CSF cultures, it is often self-limiting without treatment.
3.Fungal meningitis: Acute fungal infection of the meninges and CSF, characterized by a moderate elevation of white blood cells in the CSF, generally with negative bacterial cultures but positive for antibodies of fungal organisms. Like bacterial meningitis, it is associated with significant morbidity and mortality.
4.Drug-induced meningitis (rare): Acute inflammation of the meninges, characterized by a moderate elevation of white blood cells in the CSF with negative blood cultures and history of using nonsteroidal anti-inflammatory drugs (NSAIDs), certain antibiotics, intravenous immune globulin, and antiepileptic drugs.
Incidence
A.In 2015, there were 8.7 million cases of meningitis worldwide.
B.More than one million cases of bacterial meningitis occur every year, worldwide.
C.Meningitis is one of the top 10 causes of death from infection. Fatalities from meningitis are in excess of 100,000 every year.
D.Like bacterial meningitis, fungal meningitis is associated with a significant morbidity and mortality.
Pathogenesis
A.Many pathogens responsible for meningitis, including bacteria, possess surface components that enhance mucosal colonization.
1.After bacterial colonization, invasion across the epithelium occurs by intra- or inter-cellular pathways, often mediated by specific adhesions of the bacterial surface.
2.Following invasion, bacteria survive normal immunological forces via evasion of the complement system, often due to polysaccharide capsules, and then cross the blood–brain barrier. Complement activation may occur in the CSF, often causing meningeal tissue damage. In the CSF, bacteria can multiply to high concentrations due to the low humoral immunity activity in CSF. The clinical disease process is due to the interaction of the host inflammatory response and bacterial components once the bacteria enter the CSF.
3.Once inflammation is present, a series of injuries to the blood–brain barrier epithelium lead to vasogenic brain edema, loss of cerebrovascular regulation, and increased intracranial pressure (ICP), ultimately leading to motor, sensory, or cognitive deficits.
B.Bacterial meningitis: Characterized as a rapidly progressing systemic bacterial illness presenting with fever, headache, and neck stiffness.
C.Cortical brain function: Generally remains intact as brain parenchyma is spared.
D.Types of meningitis and associated causal pathogens.
1.Bacterial meningitis.
a.Misdiagnosed, undiagnosed, or untreated bacterial meningitis: Associated with a high rate of morbidity and nearly 100% mortality.
b.Most common bacterial pathogens: Streptococcus pneumoniae, Listeria monocytogenes, Neisseria meningitis, Haemophilus influenzae, and Staphylococcus aureus.
i.Adults: Most common pathogen is S. pneumoniae.
ii.Elderly (age >60): Highly susceptible to L. monocytogenes.
2.Viral meningitis.
a.Diagnosis of exclusion given the limited diagnostic tools for isolating individual pathogens.
b.Most common viral pathogens: Human simplex virus (HSV), varicella-zoster virus (VZV), HIV, West Nile Virus (WNV), and enteroviruses.
3.Fungal meningitis.
a.Most common fungal pathogens: Cryptococcus neoformans and Coccidioides immitis.
4.Drug-induced meningitis.
a.Proposed mechanism of action: Combination of delayed hypersensitivity reaction and direct meningeal irritation.
b.Common causative agents: NSAIDs, certain antibiotics, intravenous immune globulin, and antiepileptic drugs.
Predisposing Factors
A.Immunocompromised state.
B.Use of immunosuppressive therapy.
C.Organ transplantation.
D.Environmental exposure.
E.Use of intravenous drugs.
F.Lack of immunizations for meningococcus (Neisseria meningitides), pneumococcus (S. pneumoniae), and H. influenzae.
G.Recent brain surgery or trauma (concern for S. aureus).
H.Bacterial meningitis is more likely to affect the elderly and individuals who are immunocompromised.
Subjective Data
A.Common complaints/symptoms.
1.Severe headache.
2.Nuchal rigidity: Inability to flex neck forward passively due to increased muscle tone and stiffness; present in 70% of cases of bacterial meningitis.
3.Hyperthermia/hypothermia.
4.Altered mental status.
B.Common/typical scenario.
1.Classic triad of meningitis: Fever, neck stiffness, and headaches.
a.Found in less than 50% of patients.
b.However, two out of three symptoms should raise suspicion for meningitis.
2.Nonspecific symptoms: Altered mental status, lethargy, malaise, nausea, vomiting, diarrhea, photophobia, muscle aches, cough, and sore throat.
C.Family and social history.
1.Family history: Generally noncontributory.
2.Social history: Recent illness; travel abroad, particularly sub-Saharan Africa; exposure to rodents, ticks, mosquitos; or individuals residing in close quarters (e.g., students in dormitory housing).
3.Medication history positive for NSAIDs, certain antibiotics, intravenous immune globulin, or antiepileptic drugs.
D.Review of systems.
1.General: Fatigue, weakness, fever, or chills.
2.Head, ear, eyes, nose, and throat (HEENT): Head-aches, neck pain, or neck stiffness.
3.Neurological: Lethargy.
4.Skin: Rash.
Physical Examination
A.Nuchal rigidity, including tenderness to palpation and pain with flexion or extension.
B.Kernig test: Pain induced by attempting full extension of the knee while the hip is flexed at 90°. Specificity is high, but sensitivity is limited.
C.Brudzinski test: Passive flexion of the neck induces flexion of the hips. Specificity is high, but sensitivity is limited.
D.Lethargy and suppressed level of consciousness.
E.Focal neurological deficits, including cranial nerve palsies.
F.Papilledema.
G.Petechial or ecchymotic rash. Petechial rash is relatively specific for meningococcal meningitis, which is caused by N. meningitides.
Diagnostic Tests
A.Lumbar puncture: Gold standard for diagnosis of bacterial meningitis (ideally performed prior to or simultaneously with antibiotic administration) with CSF analysis.
1.CSF analysis.
a.Assessment of cell count/differential, glucose, protein gram stain, and bacterial culture.
b.Normal CSF.
i.Normal opening pressure less than 20 mmHg.
ii.CSF WBC less than 5/μL.
iii.CSF RBC (absent).
1)CSF Glucose greater than 60 mg/dL and CSF/serum ratio of greater than 0.6.
iv.CSF Protein less than 50 mg/dL.
v.Sterile culture.
c.Abnormal CSF suggestive of bacterial meningitis.
i.Elevated opening pressure.
ii.CSF WBC greater than 1,000/μL and neutrophil dominant.
iii.CSF RBC (absent).
iv.CSF Glucose less than 40 mg/dL and CSF/serum ratio of less than 0.4.
v.CSF Protein greater than 200 mg/dL.
vi.Culture results in a positive growth for bacterial organism.
d.Abnormal CSF suggestive of viral/aseptic meningitis.
i.Elevated opening pressure.
ii.CSF WBC less than 250/μL and lymphocyte dominant.
iii.CSF RBC (absent).
iv.CSF Glucose greater than 60 mg/dL.
v.CSF Protein less than 150 mg/dL.
vi.Sterile culture.
e.Abnormal CSF suggestive of fungal meningitis (results may be nonspecific).
i.Elevated opening pressure.
ii.CSF WBC less than 500/μL and lymphocyte dominant.
iii.CSF RBC (absent).
iv.CSF Glucose less than 40 mg/dL and CSF/serum ratio of less than 0.4.
1)Bacteria ingest glucose, causing a decreased level associated with bacterial meningitis.
v.CSF Protein greater than 250 mg/dL.
vi.Sterile culture.
1)Proceed with fungal cultures and fungal antibody testing.
f.WBC/RBC adjustment.
i.A false positive WBC elevation: Often noted in a traumatic lumbar puncture or a patient with subarachnoid bleed.
ii.Acceptable ratio of WBC/RBC should be approximately 1:700.
2.Relative contraindications to lumbar puncture.
a.Systemic anticoagulation.
b.Thrombocytopenia.
c.Coagulopathy.
d.Open sacral wound at level L3 to L5.
e.CT of the head with evidence of increased ICP and/or mass lesion.
B.Laboratory tests.
1.Relevant blood work including complete blood count (CBC), basal metabolic profile (BMP), partial thromboplastin time (PTT)/prothrombin time (PT)/international normalized ratio (INR), lactate, and arterial blood gas.
2.Blood cultures.
C.A noncontrast CT of the head: Required for certain patients.
1.Those who present with signs and symptoms concerning for elevated ICP, altered level of consciousness, new-onset seizures, or focal neurological deficits.
2.Those with immunocompromised status.
3.Those with a history of prior central nervous system (CNS) infection, trauma, stroke, cancer, and surgery.