From the Guidelines
Elevated cerebrospinal fluid (CSF) protein levels are primarily caused by blood-brain barrier disruption, increased protein synthesis within the central nervous system during inflammation, obstruction of CSF flow, and decreased CSF production, as well as conditions such as meningitis, Guillain-Barré syndrome, and certain neuropathies, as noted in a study published in Nature Reviews Neurology in 2019 1. The mechanisms leading to elevated CSF protein levels can be understood by considering the various pathways through which proteins can enter or accumulate in the CSF.
- Blood-brain barrier disruption allows plasma proteins to leak into the CSF, a common occurrence in conditions like meningitis and Guillain-Barré syndrome.
- Increased protein synthesis within the central nervous system during inflammation is another mechanism, as seen in infectious and inflammatory diseases.
- Obstruction of CSF flow impairs protein clearance, leading to elevated levels.
- Decreased CSF production concentrates existing proteins, further contributing to elevated levels. Specific conditions associated with elevated CSF protein include:
- Meningitis
- Guillain-Barré syndrome, where albumino-cytological dissociation (elevated protein with normal cell count) is a classic finding, although protein levels may be normal in the first week in 30-50% of patients and in the second week in 10-30% of patients 1.
- Multiple sclerosis
- Brain tumors
- Spinal cord compression
- Certain neuropathies Blood contamination during lumbar puncture (traumatic tap) can also falsely elevate CSF protein readings, as discussed in guidelines for managing suspected viral encephalitis in adults and children 1. The normal CSF protein range is typically 15-45 mg/dL, with levels above this threshold considered elevated. The degree of elevation can provide diagnostic clues, with infectious processes often causing moderate increases, while conditions like Guillain-Barré syndrome may produce markedly high levels, highlighting the importance of interpreting CSF results in the context of clinical presentation and other diagnostic findings 1.
From the Research
Mechanisms Leading to Elevated CSF Protein Levels
Elevated cerebrospinal fluid (CSF) protein levels can result from various mechanisms, including:
- Inflammation and blood-brain barrier (BBB) disruption, as seen in subarachnoid hemorrhage (SAH) 2
- Blood-CSF barrier (BCB) damage, which correlates with the clinical course of Guillain-Barré syndrome (GBS) and chronic inflammatory polyradiculoneuropathy (CIP) 3
- Decrease of CSF flow rate, which can explain the increase of CSF protein concentrations in many neurological diseases 4
- Intrathecal IgG synthesis, although studies suggest that oligoclonal IgG in CSF comes essentially from serum 3
Associated Conditions
Elevated CSF protein levels have been associated with:
- Poor outcome after spontaneous SAH 2
- Severity of GBS and development of BCB damage 3
- Delayed radiographic infarction on 3 to 12-month neuroimaging 2
- Neuroborreliosis, although the incidence of elevated antibodies is highest in this condition 5