ABSTRACT
BACKGROUND: The progressive phase of multiple sclerosis (MS) is characterized by an intrathecal (IT) compartmentalization of inflammation, involving B-cells within meningeal follicles, and resisting all the available immunosuppressive treatments. A new therapeutic paradigm may be to target this inflammation by injecting immunosuppressive drugs inside the central nervous system compartment. METHODS: We designed a single-center, open-label, randomized, controlled, phase II study designed to evaluate the safety and efficacy of IT rituximab in progressive MS (EFFRITE trial; ClinicalTrial Registration NCT02545959). Patients were randomized into three arms (1 : 1 : 1): control group, IT rituximab (20 mg, IT) group, and intravenous+IT (IV+IT) group. The main outcome was a change in levels of CSF biomarkers of inflammation (osteopontin). Secondary outcomes were changes in levels of CSF biomarkers of axonal loss (neurofilament light chain) and clinical and MRI changes. RESULTS: Ten patients were included (2 : 4 : 4). No adverse event occurred. OPN level remained stable in CSF at each time point, whereas NFL had slightly decreased (-8.7%) at day 21 (p = 0.02). Clinical parameters remained stable and leptomeningeal enhancements remained unchanged. CONCLUSION: Clinical outcome and biomarkers of inflammation were not dramatically modified after IT injection of rituximab, probably due to its limited efficiency in CSF. Drug issues for future studies are discussed.
ABSTRACT
Recent studies identified chronic leptomeningeal enhancement (LME) in late-acquired FLAIR sequences in secondary progressive (SP) multiple sclerosis (MS). These LMEs correlate with focal cortical inflammation and demyelination observed by pathology, which are supposed to drive long-term cortical atrophy. We report a spontaneously remitting meningeal uptake in a patient suffering from SP MS. No cortical lesion was visible on FLAIR or DIR sequences, but the rate of cortical atrophy was higher in this area. This case suggests that conventional 3-T MRI, by contrary to white matter lesions, may be amnesic with regard to the potential burden of previous regressive meningeal lesions. Moreover, T1-enhanced sequences underscore the real inflammatory activity. LME could be more than passive markers of SP MS, but is also directly responsible for focal cortical atrophy and could be an early manifestation of cortical lesions.
