Tysabri Does Not Cause CSF Buildup
Tysabri (natalizumab) does not cause cerebrospinal fluid to build up or accumulate. Instead, the drug alters the cellular composition and protein content of CSF by reducing inflammatory markers, but does not increase CSF volume or cause hydrocephalus.
What Tysabri Actually Does to CSF
Reduces Inflammatory Markers
- Natalizumab treatment significantly decreases CSF leukocytes (white blood cells in the spinal fluid) 1
- CSF protein levels drop during treatment, reflecting reduced inflammation 1
- The albumin quotient (a measure of blood-brain barrier integrity) decreases, indicating improved barrier function 1
- IgG and IgM quotients in CSF are reduced, showing less antibody production in the central nervous system 1
Changes T-Cell Ratios
- Natalizumab alters the CD4+/CD8+ T-cell ratio in CSF by preferentially blocking CD4+ T-cells from entering the CNS 2
- This occurs because CD4+ T-cells express more alpha-4 integrin (the target of natalizumab) compared to CD8+ T-cells 2
- The CSF CD4+/CD8+ ratio normalizes within 6 months after stopping natalizumab 2
Reduces Neurodegeneration Markers
- CSF concentrations of 24-hydroxycholesterol (a marker of neuronal damage) decrease with natalizumab treatment, indicating reduced neurodegeneration 3
- CSF concentrations of 27-hydroxycholesterol also decrease, reflecting improved blood-brain barrier integrity 3
Important Clinical Context
CSF Testing in Natalizumab-Treated Patients
The main reason for CSF examination in patients on Tysabri is surveillance for progressive multifocal leukoencephalopathy (PML), a rare but serious viral infection 4
- CSF is tested for JC virus DNA when PML is suspected 4
- Early viral loads may be below detection limits, requiring repeat testing if clinical suspicion remains high 4
What This Means for Practice
- If a patient on Tysabri has symptoms suggesting increased intracranial pressure or hydrocephalus, look for alternative causes rather than attributing it to the medication 4, 1
- The drug's mechanism of action (blocking alpha-4 integrin) prevents immune cells from crossing the blood-brain barrier but does not affect CSF production or drainage 2