Fig. 2

The blood–brain barrier and the effects of intravenous rituximab, intravenous methotrexate, and intrathecal methotrexate within it. Intravenous rituximab is a large molecule that is unable to cross from blood vessels to within the CSF in the subarachnoid space or into the brain parenchyma. However, they exert their cytotoxic effect within the blood supply in these areas and hence minimize CNS relapses. Intravenous methotrexate is a small molecule and therefore can cross the blood–brain barrier, exerting their cytotoxic effect within the brain parenchyma and to a certain extent within the CSF in the subarachnoid space as well. Intrathecal methotrexate enters the CSF within the subarachnoid space directly and may even cross the blood–brain barrier into the brain parenchyma. However, intrathecal administration does not guarantee uniformly consistent drug levels, especially when crossing through the blood–brain barrier, impairing the efficacy of its cytotoxic effect