Dramatic rebounds of MS during pregnancy following fingolimod withdrawal

Abstract

In MS, discontinuation of some therapies may result in a transitory, possibly overwhelming, increase in disease activity.1–4 We report 2 cases of severe clinical rebound after fingolimod suspension occurring in 2 patients following pregnancy. Clinical rebound was defined as the occurrence of new severe neurologic symptoms together with a significant increase of new or enlarging T2-weighted or gadolinium-enhancing T1-weighted lesions exceeding baseline activity, on treatment discontinuation.4 The first patient was diagnosed with MS in 2005. In the subsequent 3 years, she experienced several relapses and progressive increase of MRI lesion load despite the sequential introduction of weekly interferon-β1a, thrice weekly interferon-β1a and then glatiramer acetate. Natalizumab (NTZ) was then started (EDSS 3.0, JCV antibodies negative status), resulting in no evidence of disease activity for the following 40 months. On seroconversion, NTZ was interrupted in August 2011 beacause of the potential risk of progressive multifocal leukoencephalopathy (PML) and fingolimod was started. In March 2013, fingolimod was suspended as disease was stable (figure, A) and due to desire of pregnancy and potential risks of fetal exposure to fingolimod.5 Lymphocyte count was 0.34 × 109/L. In April 2013, she resulted pregnant. In July (eleventh week of pregnancy), she abruptly developed quadriplegia and signs of severe cognitive impairment (EDSS: 9.0). Lymphocyte count was 1.54 × 109/L. One gram of methylprednisolone was administered IV for 5 days with partial recovery (EDSS 7.0). One month later, she developed locked-in syndrome (EDSS 9.5). Brain MRI showed a dramatic increase of white-matter abnormalities with many gadolinium-enhancing lesions (figure, B). PML was excluded by CSF analysis. IV methylprednisolone followed by IV immunoglobulins were administered with no success. Plasma exchange was not considered because of the possible adverse effects on maternal hemodynamics and limited experience on pregnant patients with MS. On therapeutic abortion, she received IV cyclophosphamide (2 g/m2), improving clinically (EDSS 7.0) and radiologically (figure, C). One month later, her clinical condition deteriorated (EDSS 8.0) with worsening of brain MRI (figure, D). She was treated again with IV cyclophosphamide (1 g/m2), but a few days later, she developed septic shock and died.