ObjectiveTo determine baseline cerebrospinal fluid and magnetic resonance imaging (MRI) variables at the onset of a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) that predict evolution to secondary progressive MS (SPMS).Methods276 CIS patients with a minimum follow-up of 10 years were studied. Baseline presence of oligoclonal IgG and IgM bands (OCGB and OCMB respectively); number of brain T2 lesions (B-T2L), brain gadolinium enhancement lesions (brain-GEL), cervical spinal cord T2 lesions (cSC-T2L); and fulfillment of 2017 McDonald criteria among other variables were collected.Results14 patients ended up with a non-MS condition. 138/276 CIS patients fulfilled 2017 McDonald criteria. Mean age was 32.4 years, 185 female. 227 received treatment, 95 as CIS. After a mean follow-up of 12 years, 36 patients developed SPMS. Conversion to SPMS was associated with OCGB (p = 0.02), OCMB (p = 0.0001); ≥ 9 B-T2L (p = 0.03), brain-GEL (p = 0.03), and cSC-T2L (p = 0.03). However, after adjusting for sex, age, BT2L, brain-GEL, SC-T2, and OCMB status, only OCMB (HR 4.4, 1.9–10.6) and cSC-T2L (HR 2.2, 1.0–6.2) suggested an independent association with risk of conversion to SPMS. Patients with both risk factors had a HR of 6.12 (2.8–12.9).DiscussionOCMB and SC-T2 lesions are potential independent predictors of conversion to SPMS.
BackgroundInaccessibility of inflammation compartmentalised to the CNS may underlie the lack of effectiveness of immunomodulatory treatments in progressive multiple sclerosis (PMS), turning its treatment into a challenge for researches. Intrathecal rituximab (IT-RTX) is a new treatment option which has shown promising results in clinical trials but clinical experience is limited.1
PurposeCase report of the use and outcomes in 3 patients with PMS treated with IT-RTX in a tertiary hospital.Material and methods3 cases of PMS are reported: patient A (man), patient B (man) and patient C (woman) aged 44, 48 and 42 years, respectively. All patients were treated with IT-RTX. Effectiveness and safety of IT-RTX were evaluated. Demographic and clinical data were collected from patients’ electronic medical records. All patients started IT-RTX treatment following a compassionate use clinical study protocol, after hospital approval and informed consent was obtained.ResultsAll patients received weekly 25 mg doses of IT-RTX, over a 3 week period. Patient B also received a fourth dose of 25 mg 8 months after the first dose. Flow cytometry was performed on peripheral blood (table), revealing a remarkable effect on peripheral B lymphocytes CD45 and CD19, with undetectable levels of CD19. Similar depletion was observed with peripheral B lymphocytes CD3, CD4, CD8 and CD16+CD56. This effect was maintained over time, rising again after several months without treatment.No changes in the Expanded Disability Status Scale (EDSS) were observed (table), except for patient B, who developed a slight improvement. The treatment was well tolerated, although patient B suffered a fever episode after the first dose and patient C died from massive pulmonary embolism, a rare RTX related complication, 5 months after finishing treatment.No ADM
Patient A
Patient B
Patient C
CD45
I1045II2285III111410141517*157911751901
CD19
I123II5III000*37841EDSS-pre8.56.56.5EDSS-post8.56.06.5*Post-treatment analysis: 5 months (patient A), 6 months (patient B), 2 months (patient C) after the last dose.ConclusionIn our patients, IT-RTX showed limited effectiveness, with disease stabilisation (similar EDSS) and depletion of peripheral B lymphocytes (especially CD19). Although the treatment was well tolerated, a rare and severe adverse event was reported.References and/or acknowledgements1. Svenningsson. Neurol Neuroimmunol Neuroinflamm2015;2:e79.No conflict of interest
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