From the Guidelines
A higher than normal cerebrospinal fluid (CSF) protein level is a symptom of an underlying condition, such as inflammation or disruption of the blood-brain barrier, and requires further diagnostic testing to determine the cause. The normal CSF protein range is between 15-45 mg/dL, and elevated levels can suggest various conditions, including meningitis, multiple sclerosis, Guillain-Barré syndrome, brain tumors, or neurodegenerative diseases, as seen in patients with Guillain-Barré syndrome, where the combination of an elevated CSF protein level and a normal CSF cell count is a classic finding 1. The degree of elevation can provide diagnostic clues, with moderate increases (50-100 mg/dL) possibly indicating demyelinating diseases, and significant elevations (>100 mg/dL) often suggesting infection or malignancy, although the presence of a normal opening pressure, few white blood cells, and a normal CSF protein concentration can essentially exclude meningitis 1. Some key points to consider when evaluating elevated CSF protein levels include:
- The timing of the elevation, as protein levels may be normal in the early stages of certain diseases, such as Guillain-Barré syndrome 1
- The presence of other CSF abnormalities, such as pleocytosis or low glucose levels, which can suggest specific underlying conditions 1
- The need for further diagnostic testing, including CSF culture, cytology, oligoclonal bands, and imaging studies, to determine the underlying cause of the elevated CSF protein level. Treatment should focus on addressing the underlying cause rather than the protein elevation itself, as it is a symptom rather than a disease.
From the Research
Higher than Normal CSF Protein
A higher than normal cerebrospinal fluid (CSF) protein level can be an indicator of various conditions affecting the central nervous system. Some of the possible causes of elevated CSF protein include:
- Inflammation and blood-brain barrier disruption, as seen in subarachnoid hemorrhage 2
- Spinal stenosis and arterial hypertension, which were associated with higher CSF protein levels in a population-based study 3
- Increasing age, male sex, and diabetes, which were independently associated with higher CSF protein levels in a multivariable analysis 3
- Central nervous system infection, such as bacterial or viral meningitis, which can cause changes in CSF white blood cell counts, CSF protein levels, and the CSF:serum glucose ratio 4
- Subarachnoid hemorrhage, which has a high mortality rate and can be diagnosed using CSF analysis, including the presence of xanthochromia and an elevated red blood cell count 4, 5
Reference Ranges for CSF Protein
The normal range for CSF protein can vary depending on the laboratory and the population being studied. A study found that the mean CSF protein level was 52.2 mg/dL, with a 95% reference interval of 24.0 to 93.4 mg/dL 3. Another study suggested that higher upper reference limits for CSF protein should be considered worldwide, particularly for older adults 6.
Clinical Implications
Elevated CSF protein levels can have significant clinical implications, including: