Thrombolysis Experience in Costa Rica Compared Against Individual Patient Data from two Randomized Controlled Trials.

OBJECTIVES: We sought to compare thrombolysis outcomes from the Costa Rican Stroke Registry Program (CRSRP) with published individual patient data from NINDS and CLOTBUST-ER trials using matching and outcome modeling from randomized clinical trials (RCTs). MATERIALS AND METHODS: A retrospective observational study matching subjects on baseline characteristics, from the CRSRP, the control arm of CLOTBUST-ER, and the interventional arm of NINDS trials. Day 7-10/discharge modified Rankin Score (mRS), and early mortality was compared between matched subjects. A mortality model derived from RCTs was developed, and outcomes were compared at similar baseline NIHSS scores. CRSRP symptomatic hemorrhage (SICH) rate was compared with an Ibero-American cohort (IAC). RESULTS: Of 540 CRSRP patients, 351 received rt-PA under 3 hours and were matched with NINDS subjects yielding 292 pairs; 161 CRSRP subjects treated within 4.5 hours were matched with CLOTBUST-ER subjects resulting in 151 pairs. The proportion of patients achieving excellent outcomes (mRS 0-1) did not differ between CRSRP and either NINDS or CLOTBUST-ER (CRSRP vs NINDS: 36.6% vs 32.9%, p=0.3; CRSRP vs CLOTBUST-ER: 26.5% vs 24.5%, p=0.8). Mortality was higher for CRSRP vs CLOTBUST-ER (7.3% vs 0.7%, p=0.006), but not vs NINDS (6.5% vs 4.5%, p=0.4). A pooled mortality model derived from 15 RCTs representing 4410 patients (R2=0.39) showed CRSRP and NINDS within expected mortality, while CLOTBUST-ER showed lower than expected mortality. CRSRP SICH rate equaled IAC (5.7% vs 5.7%; p=0.9). CONCLUSIONS: Functional outcomes and SICH of thrombolysed Costa Rican patients compared favorably with published datasets, with a potential increase in early mortality.

Acute relapse after initiation of Siponimod in a patient with secondary progressive MS.

Sphingosine 1-phosphate (S1P) is a signaling molecule that binds to five G protein-coupled receptors (Proc Natl Acad Sci USA 108:751-756, 2011). Modulation of these receptors has been associated with pleiotropic biological effects in the immune, cardiovascular, and central nervous systems (CNS). The functional S1P receptor antagonist fingolimod was the first member of this class of pharmacotherapeutics to be approved for treatment of relapsing multiple sclerosis (MS). Siponimod is currently in clinical trial in patients with secondary progressive (SP) MS, a clinical trial for which there is an unmet need for disease-modifying agents. 10 weeks into the trial, the patient awoke with blurry vision in his left eye, and was subsequently diagnosed with an acute optic neuritis. Despite discontinuation of siponimod and treatment with pulse corticosteroids, the patient did not regain visual function in the affected eye. This is the first report of disease reactivation shortly after initiating siponimod in a patient with SPMS. This case illustrates that the known changes in lymphocyte numbers and composition in the CNS associated with S1P receptor antagonism during the SPMS disease stage may have adverse outcomes in some patients during treatment initiation, and that close clinical and paraclinical monitoring is advised.