Kevin Messacar1, Stefan Sillau2, Sarah E Hopkins2, Catherine Otten2, Molly Wilson-Murphy2, Brian Wong2, Jonathan D Santoro2, Andrew Treister2, Harlori K Bains2, Alcy Torres2, Luke Zabrocki2, Julia R Glanternik2, Amanda L Hurst2, Jan A Martin2, Teri Schreiner2, Naila Makhani2, Roberta L DeBiasi2, Michael C Kruer2, Adriana H Tremoulet2, Keith Van Haren2, Jay Desai2, Leslie A Benson2, Mark P Gorman2, Mark J Abzug2, Kenneth L Tyler2, Samuel R Dominguez2. 1. From the Departments of Pediatrics (K.M., J.A.M., T.S., M.J.A., S.R.D.) and Neurology (K.M., S.S., J.A.M., T.S., K.L.T.), University of Colorado School of Medicine; Children's Hospital Colorado (K.M., A.L.H., J.A.M., T.S., M.J.A., S.R.D.), Aurora; Children's Hospital of Philadelphia (S.E.H.), PA; Seattle Children's Hospital (C.O.), University of Washington; Boston Children's Hospital (M.W.-M., L.A.B., M.P.G.), MA; Children's Hospital of Los Angeles (B.W., J.D.), CA; Stanford University (J.D.S., K.V.H.), Palo Alto, CA; University of California San Diego (A.T., A.H.T.); Phoenix Children's Hospital (H.K.B., M.C.K.), AZ; Boston Medical Center (A.T.), MA; Naval Medical Center of San Diego (L.Z.), CA; Departments of Pediatrics (J.R.G., N.M.) and Neurology (N.M.), Yale School of Medicine, New Haven, CT; and Children's National Medical Center (R.L.D.), Washington, DC. kevin.messacar@childrenscolorado.org. 2. From the Departments of Pediatrics (K.M., J.A.M., T.S., M.J.A., S.R.D.) and Neurology (K.M., S.S., J.A.M., T.S., K.L.T.), University of Colorado School of Medicine; Children's Hospital Colorado (K.M., A.L.H., J.A.M., T.S., M.J.A., S.R.D.), Aurora; Children's Hospital of Philadelphia (S.E.H.), PA; Seattle Children's Hospital (C.O.), University of Washington; Boston Children's Hospital (M.W.-M., L.A.B., M.P.G.), MA; Children's Hospital of Los Angeles (B.W., J.D.), CA; Stanford University (J.D.S., K.V.H.), Palo Alto, CA; University of California San Diego (A.T., A.H.T.); Phoenix Children's Hospital (H.K.B., M.C.K.), AZ; Boston Medical Center (A.T.), MA; Naval Medical Center of San Diego (L.Z.), CA; Departments of Pediatrics (J.R.G., N.M.) and Neurology (N.M.), Yale School of Medicine, New Haven, CT; and Children's National Medical Center (R.L.D.), Washington, DC.
Abstract
OBJECTIVE: To determine the safety, tolerability, and efficacy of fluoxetine for proven or presumptive enterovirus (EV) D68-associated acute flaccid myelitis (AFM). METHODS: A multicenter cohort study of US patients with AFM in 2015-2016 compared serious adverse events (SAEs), adverse effects, and outcomes between fluoxetine-treated patients and untreated controls. Fluoxetine was administered at the discretion of treating providers with data gathered retrospectively. The primary outcome was change in summative limb strength score (SLSS; sum of Medical Research Council strength in all 4 limbs, ranging from 20 [normal strength] to 0 [complete quadriparesis]) between initial examination and latest follow-up, with increased SLSS reflecting improvement and decreased SLSS reflecting worsened strength. RESULTS: Fifty-six patients with AFM from 12 centers met study criteria. Among 30 patients exposed to fluoxetine, no SAEs were reported and adverse effect rates were similar to unexposed patients (47% vs 65%, p = 0.16). The 28 patients treated with >1 dose of fluoxetine were more likely to have EV-D68 identified (57.1% vs 14.3%, p < 0.001). Their SLSS was similar at initial examination (mean SLSS 12.9 vs 14.3, p = 0.31) but lower at nadir (mean SLSS 9.25 vs 12.82, p = 0.02) and latest follow-up (mean SLSS 12.5 vs 16.4, p = 0.005) compared with the 28 patients receiving 1 (n = 2) or no (n = 26) doses. In propensity-adjusted analysis, SLSS from initial examination to latest follow-up decreased by 0.2 (95% confidence interval [CI] -1.8 to +1.4) in fluoxetine-treated patients and increased by 2.5 (95% CI +0.7 to +4.4) in untreated patients (p = 0.015). CONCLUSION: Fluoxetine was well-tolerated. Fluoxetine was preferentially given to patients with AFM with EV-D68 identified and more severe paralysis at nadir, who ultimately had poorer long-term outcomes. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with EV-D68-associated AFM, fluoxetine is well-tolerated and not associated with improved neurologic outcomes.
OBJECTIVE: To determine the safety, tolerability, and efficacy of fluoxetine for proven or presumptive enterovirus (EV) D68-associated acute flaccid myelitis (AFM). METHODS: A multicenter cohort study of US patients with AFM in 2015-2016 compared serious adverse events (SAEs), adverse effects, and outcomes between fluoxetine-treated patients and untreated controls. Fluoxetine was administered at the discretion of treating providers with data gathered retrospectively. The primary outcome was change in summative limb strength score (SLSS; sum of Medical Research Council strength in all 4 limbs, ranging from 20 [normal strength] to 0 [complete quadriparesis]) between initial examination and latest follow-up, with increased SLSS reflecting improvement and decreased SLSS reflecting worsened strength. RESULTS: Fifty-six patients with AFM from 12 centers met study criteria. Among 30 patients exposed to fluoxetine, no SAEs were reported and adverse effect rates were similar to unexposed patients (47% vs 65%, p = 0.16). The 28 patients treated with >1 dose of fluoxetine were more likely to have EV-D68 identified (57.1% vs 14.3%, p < 0.001). Their SLSS was similar at initial examination (mean SLSS 12.9 vs 14.3, p = 0.31) but lower at nadir (mean SLSS 9.25 vs 12.82, p = 0.02) and latest follow-up (mean SLSS 12.5 vs 16.4, p = 0.005) compared with the 28 patients receiving 1 (n = 2) or no (n = 26) doses. In propensity-adjusted analysis, SLSS from initial examination to latest follow-up decreased by 0.2 (95% confidence interval [CI] -1.8 to +1.4) in fluoxetine-treated patients and increased by 2.5 (95% CI +0.7 to +4.4) in untreated patients (p = 0.015). CONCLUSION: Fluoxetine was well-tolerated. Fluoxetine was preferentially given to patients with AFM with EV-D68 identified and more severe paralysis at nadir, who ultimately had poorer long-term outcomes. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with EV-D68-associated AFM, fluoxetine is well-tolerated and not associated with improved neurologic outcomes.
Authors: Rachel Ulferts; Lonneke van der Linden; Hendrik Jan Thibaut; Kjerstin H W Lanke; Pieter Leyssen; Bruno Coutard; Armando M De Palma; Bruno Canard; Johan Neyts; Frank J M van Kuppeveld Journal: Antimicrob Agents Chemother Date: 2013-01-18 Impact factor: 5.191
Authors: Kevin Messacar; Teri L Schreiner; Keith Van Haren; Michele Yang; Carol A Glaser; Kenneth L Tyler; Samuel R Dominguez Journal: Ann Neurol Date: 2016-08-04 Impact factor: 10.422
Authors: James J Sejvar; Adriana S Lopez; Margaret M Cortese; Eyal Leshem; Daniel M Pastula; Lisa Miller; Carol Glaser; Anita Kambhampati; Kayoko Shioda; Negar Aliabadi; Marc Fischer; Nicole Gregoricus; Robert Lanciotti; W Allan Nix; Senthilkumar K Sakthivel; D Scott Schmid; Jane F Seward; Suxiang Tong; M Steven Oberste; Mark Pallansch; Daniel Feikin Journal: Clin Infect Dis Date: 2016-06-17 Impact factor: 9.079
Authors: Rami Musharrafieh; Chunlong Ma; Jiantao Zhang; Yanmei Hu; Jessica M Diesing; Michael T Marty; Jun Wang Journal: J Virol Date: 2019-03-21 Impact factor: 5.103
Authors: Olwen C Murphy; Kevin Messacar; Leslie Benson; Riley Bove; Jessica L Carpenter; Thomas Crawford; Janet Dean; Roberta DeBiasi; Jay Desai; Matthew J Elrick; Raquel Farias-Moeller; Grace Y Gombolay; Benjamin Greenberg; Matthew Harmelink; Sue Hong; Sarah E Hopkins; Joyce Oleszek; Catherine Otten; Cristina L Sadowsky; Teri L Schreiner; Kiran T Thakur; Keith Van Haren; Carolina M Carballo; Pin Fee Chong; Amary Fall; Vykuntaraju K Gowda; Jelte Helfferich; Ryutaro Kira; Ming Lim; Eduardo L Lopez; Elizabeth M Wells; E Ann Yeh; Carlos A Pardo Journal: Lancet Date: 2020-12-23 Impact factor: 79.321
Authors: Lisa Bauer; Roberto Manganaro; Birgit Zonsics; Jeroen R P M Strating; Priscila El Kazzi; Moira Lorenzo Lopez; Rachel Ulferts; Clara van Hoey; Maria J Maté; Thierry Langer; Bruno Coutard; Andrea Brancale; Frank J M van Kuppeveld Journal: ACS Infect Dis Date: 2019-07-31 Impact factor: 5.084
Authors: Jelte Helfferich; Marjolein Knoester; Coretta C Van Leer-Buter; Rinze F Neuteboom; Linda C Meiners; Hubert G Niesters; Oebele F Brouwer Journal: Eur J Pediatr Date: 2019-07-23 Impact factor: 3.183