From the Guidelines
Mild elevation of protein in cerebrospinal fluid (CSF) is most likely caused by conditions such as Guillain-Barré syndrome, infections, inflammatory disorders, or autoimmune conditions, as evidenced by the most recent study 1. The causes of mild elevated protein in CSF can be varied, including:
- Infections like meningitis, encephalitis, or neurosyphilis
- Inflammatory disorders such as multiple sclerosis or Guillain-Barré syndrome
- Autoimmune conditions
- Certain cancers that involve the brain or spinal cord
- Blood in the CSF from trauma or hemorrhage
- Degenerative neurological diseases like Alzheimer's disease
- Some medications or contrast agents used in diagnostic procedures
- Normal aging
According to the study 1, the classic finding in Guillain-Barré syndrome is the combination of an elevated CSF protein level and a normal CSF cell count, known as albumino-cytological dissociation. However, protein levels are normal in 30–50% of patients in the first week after disease onset and 10–30% of patients in the second week. The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults 1 suggests that bacterial meningitis tends to have a higher CSF protein than viral meningitis, and a patient is unlikely to have bacterial disease if the CSF protein is less than 0.6 g/L. Management of suspected viral encephalitis in adults 1 also notes that a mildly elevated CSF protein can be seen in viral encephalitis, and CSF lactate may be helpful in distinguishing bacterial meningitis from viral CNS infections. Therefore, when mild elevation of protein in CSF is detected, further diagnostic testing is typically needed to determine the underlying cause, which may include additional CSF analysis, imaging studies, or blood tests depending on the clinical presentation 1. Key considerations in the interpretation of CSF results include:
- The clinical presentation of the patient
- The presence of other CSF abnormalities, such as pleocytosis or low glucose ratio
- The results of other diagnostic tests, such as imaging studies or blood tests
- The potential for alternative diagnoses, such as infectious causes of polyradiculitis.
From the Research
Causes of Mild Elevated Protein in CSF
- Guillain-Barré syndrome (GBS) has been associated with elevated protein levels in cerebrospinal fluid (CSF) 2, 3, 4
- Intravenous immunoglobulin (IVIG) therapy, often used to treat GBS, can cause aseptic meningitis, leading to elevated protein levels in CSF 2
- Demyelinating disorders, such as multiple sclerosis and GBS, can cause changes in CSF lipid concentrations, which may be correlated with elevated protein levels 3
- Combined therapy of methylprednisolone and IVIg in GBS patients may cause side effects, including transient liver function disturbances, but its effect on CSF protein levels is not clearly established 5
- Immunomodulatory therapies, including high-dose corticosteroids, plasmapheresis, and intravenous immunoglobulins, are used to treat various neurologic disorders, but their impact on CSF protein levels is not fully understood 4