Doctors start with a physical examination and a medical history. This examination may occur in the emergency room as symptoms may suddenly appear and rapidly worsen over several hours to a couple of days. Of interest to the doctor are recent illnesses, exposure to animals, mosquitoes, or ticks, contact with other people who have become ill, recent travel – especially outside of the United States, and recent activities. The doctor will note the presence or absence of signs and symptoms frequently associated with meningitis and encephalitis. Neurological examinations may be performed to assess the status of the patient’s nervous system, their sensory and motor function, coordination, vision, hearing, strength and mental status.

Laboratory Tests
Laboratory tests are performed to detect, identify, evaluate, and monitor meningitis and encephalitis. These tests are performed in order to:

• Distinguish these infectious diseases from other conditions with similar symptoms
• Determine the cause – bacterial, viral, fungal, parasitic, or other as rapidly as possible to start and guide treatment
• Evaluate the patient’s general state of health, immune system status, current signs and symptoms, and current complications to guide symptom relief and to minimize inflammation and neurological or brain damage
• Where possible, determine the infection’s source; especially important when the causative agent may be a public health concern

Tests include:
Cerebrospinal fluid (CSF) analysis. This is a primary diagnostic tool for encephalitis and meningitis. CSF analysis is a group of common tests, and a wide variety of other tests, that can be ordered and performed on a sample of CSF fluid. CSF is collected using a procedure called a lumbar puncture or spinal tap.

Initial CSF tests—The initial basic set of CSF tests that are often performed with suspected infections of the central nervous system include:

• Physical characteristics. Normal CSF appears clear and colorless. The appearance of the sample of CSF is usually compared to a sample of water. In infections, the initial pressure of CSF during collection may be increased, and the sample may appear cloudy due to the presence of white blood cells (WBCs) or microorganisms.
• CSF protein. Only a small amount is normally present in CSF because proteins are large molecules and do not cross the blood/brain barrier easily. Increases in protein are commonly seen with meningitis, brain abscess, and neurosyphilis.
• CSF glucose. Normal is about 2/3 the concentration of blood glucose. Glucose levels may decrease when cells that are not normally present use up (metabolize) the glucose. These may include bacteria or cells present due to inflammation (WBCs).
• CSF total cell counts. WBCs may be increased with central nervous system (CNS) infections.
• CSF WBC differential. Small numbers of lymphocytes, monocytes (and in neonates, neutrophils) are normal in a sample of CSF. There may be:
  • an increase in neutrophils with a bacterial infection
  • an increase in lymphocytes with a viral infection
  • sometimes an increase in eosinophils with a parasitic infection
• CSF Gram stain for direct observation of microorganisms
• CSF culture and sensitivity for bacteria, fungi, and viruses

Additional or follow-up CSF tests—If any of the initial tests are abnormal, then additional infectious testing may be ordered. This may include one or more of the following:

• Detection of viruses by PCR – detection of viral genetic material (DNA, RNA) such as herpes and enteroviruses.
• CSF Cryptococcal antigen – to detect a specific fungal infection
• Other CSF antigen tests – depending on which organism(s) are suspected
• Specific CSF antibody tests – depending on which organism(s) are suspected

Less commonly ordered CSF infectious diseases tests include:

• CSF AFB smear and culture (when tuberculosis is suspected) – positive with tuberculosis and with other mycobacteria
• CSF Molecular tests to detect Mycobacteria tuberculosis
• CSF syphilis testing (VDRL) – positive with neurosyphilis; negative does not rule out condition

Several other types of CSF testing may occasionally be ordered to help distinguish between viral and bacterial meningitis:

• CSF lactic acid—often used to distinguish between viral and bacterial meningitis. The level will usually be increased with bacterial and fungal meningitis while it will remain normal or only slightly elevated with viral meningitis.
• CSF lactate dehydrogenase (LD)—used to differentiate between bacterial and viral meningitis.
• CSF C-reactive protein (CRP) is an acute phase reactant and is elevated with inflammation. It is markedly increased with bacterial meningitis. Since it is very sensitive even with early bacterial meningitis, it is often used to distinguish between bacterial and viral meningitis.

Laboratory tests on samples other than CSF—may be ordered along with or following CSF testing and may include:

• Blood glucose, protein, CBC (Complete Blood Count) – to evaluate and to compare with CSF levels
• Tests for antibodies in blood for a variety of viruses, such as West Nile Virus. If there is a four-fold rise in the titer of the antibody between two samples collected about a month apart, then it indicates a recent infection by that microorganism.
• Blood cultures may be ordered to detect and identify bacteria in the blood.
• Cultures of other parts of the body may be performed to detect the source of the infection that led to meningitis or encephalitis.
• CMP (Comprehensive Metabolic Panel) – tests that evaluate organ function.

Non-Laboratory Tests
Imaging tests may be performed to look for signs of brain inflammation or abnormalities but may be unremarkable with encephalitis. Brain damage, tumors, bleeding, and abscesses may be detected. Tests may include:

• CT (Computed tomography)
• MRI (Magnetic Resonance Imaging)
• Ultrasound
• EEG (Electroencephalography) – to detect abnormal brain waves