The CSF normally contains very little protein because the protein in the blood plasma does not cross the blood–brain barrier easily. Protein concentration normally increases caudally from the ventricles to the cisterns and finally to the lumbar sac.

The CSF protein is a nonspecific but reliable indication of CNS pathology such as meningitis, brain abscess, MS, and other degenerative processes causing neoplastic disease. Elevated CSF protein levels may be caused by increased permeability of the blood–brain barrier, decreased resorption of the arachnoid villi, mechanical obstruction of the CSF flow, or increased intrathecal immunologic synthesis.

Results vary by level of lumbar puncture; check with the laboratory for reference values.

Total Protein

• Adults: 15–45 mg/dL or 150–450 mg/L (lumbar)

• Adults: 15–25 mg/dL or 150–250 mg/L (cisternal)

• Adults: 5–15 mg/dL or 50–150 mg/L (ventricular)

• Neonates: 15–100 mg/dL or 150–1000 mg/L (lumbar)

• Child (up to 4 years of age): 24 mg/dL (lumbar)

• Older patients (older than 60 years): 15–60 mg/dL or 150–600 mg/L (lumbar)

1. A lumbar puncture is performed (see Lumbar Puncture [Spinal Tap]).

2. Obtain 1 mL of CSF for protein analysis in a sterile screw-top tube.

3. Measure serum protein levels concurrently to interpret CSF protein values.

1. Increased CSF protein occurs in the following situations:

   1. Traumatic tap with normal CSF pressure: CSF initially streaked with blood, clearing in subsequent tubes

   2. Increased permeability of blood–CSF barrier (“influx syndrome”): CSF protein 100–500 mg/dL (1000–5000 mg/L)

      1. Infectious conditions:

         1. Bacterial meningitis: Gram stain usually positive; culture may be negative if antibiotic drugs have been administered

         2. Tuberculosis: CSF protein 50–300 mg/dL (500–3000 mg/L); mixed cellular reaction typical

         3. Fungal meningitis: CSF protein 50–300 mg/dL (500–3000 mg/L); special stains helpful

         4. Viral meningitis: CSF protein usually <200 mg/dL (<2000 mg/L)

      2. Noninfectious conditions:

         1. Subarachnoid hemorrhage: xanthochromia 2–4 hours after onset

         2. Intracerebral hemorrhage: CSF protein 20–200 mg/dL (200–2000 mg/L); marked fall in pressure after removing small amounts of CSF; xanthochromia

         3. Cerebral thrombosis: slightly increased CSF protein in 40% of cases (usually, <100 mg/dL or <1000 mg/L)

         4. Endocrine disorders, diabetic neuropathy, myxedema, hyperadrenalism, hypoparathyroidism: CSF protein 50–150 mg/dL (500–1500 mg/L) in about 50% of cases

         5. Metabolic disorders, uremia, hypercalcemia, hypercapnia, dehydration: CSF protein slightly elevated (usually, <100 mg/dL or <1000 mg/L)

         6. Drug toxicity, ethanol, phenytoin, phenothiazines: CSF protein slightly elevated in about 40% of cases (usually, <200 mg/dL or <2000 mg/L)

   3. Obstruction to circulation of CSF occurs in the following circumstances:

      1. Mechanical obstruction (e.g., tumor, abscess), herniated disk: rapid fall in pressure (yellow CSF, contains excess protein)

      2. Loculated effusion of CSF: repeated taps may show a progressive increase in CSF protein; diagnosis by myelography

   4. Increased CSF IgG synthesis occurs in the following conditions:

      1. MS: CSF protein level slightly increased

      2. SSPE: increased CSF protein

      3. Neurosyphilis: CSF protein normal or slightly increased (usually, <100 mg/dL or <1000 mg/L)

   5. Increased CSF IgG synthesis and increased permeability of blood–CSF barrier occur in the following conditions:

      1. Guillain-Barré syndrome: CSF protein usually 100–400 mg/dL (1000–4000 mg/L)

      2. Systemic autoimmune diseases: CSF protein usually <400 mg/dL (or <4000 mg/L)

      3. Chronic inflammatory demyelinating polyradiculopathy

   6. Decreased CSF protein occurs in the following conditions:

      1. Leakage of CSF due to trauma

      2. Removal of a large volume of CSF

      3. Intracranial hypertension

      4. Hyperthyroidism

      5. Young children between 6 months and 2 years of age

Pretest Patient Care

1. Follow pretest patient care for lumbar puncture (see Lumbar Puncture [Spinal Tap]).

2. Follow guidelines in Chapter 1 for safe, effective, informed pretest care.

1. Hemolyzed or xanthochromic drugs may falsely depress results.

2. Traumatic tap will invalidate the protein results.

3. see Appendix E for drugs that affect test outcomes.