Tomas Uher1, Dana Horakova2, Michaela Tyblova2, David Zeman3, Eva Krasulova2, Katerina Mrazova4, Zdenek Seidl5, Manuela Vaneckova5, Jan Krasensky5, Bianca Weinstock-Guttman6, Murali Ramanathan7, Eva Havrdova2, Robert Zivadinov8. 1. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital, Charles University in Prague, Czech Republic/Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA. 2. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital, Charles University in Prague, Czech Republic. 3. Department of Neurology, University Hospital, Ostrava, Czech Republic. 4. Department of Clinical Biochemistry, First Faculty of Medicine and General University Hospital, Charles University in Prague, Czech Republic. 5. Department of Radiology, First Faculty of Medicine and General University Hospital, Charles University in Prague, Czech Republic. 6. Department of Neurology, State University of New York, Buffalo, NY, USA. 7. Department of Neurology, State University of New York, Buffalo, NY, USA/Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, USA. 8. Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA/MR Imaging Clinical Translational Research Center, State University of New York, Buffalo, NY, USA rzivadinov@bnac.net.
Abstract
BACKGROUND: The utility of blood-brain barrier (BBB) biomarkers for clinical and magnetic resonance imaging progression in multiple sclerosis (MS) has not been extensively investigated. OBJECTIVES: To determine whether cerebrospinal fluid (CSF) measures of BBB at clinical onset predict radiological and clinical deterioration over 48 months. METHODS: This longitudinal study included 182 patients after first clinical event suggestive of MS treated with weekly intramuscular interferon beta-1a. CSF and serum samples were analyzed for leukocytes, total protein, albumin, immunoglobulins, and oligoclonal bands. Optimal thresholds for the albumin quotient (QAlb) were determined. Mixed-effect model analyses, adjusted for age, gender, and treatment escalation, were used to analyze relationship between CSF measures and disease activity outcomes over 48 months of follow-up. RESULTS: Increased QAlb at clinical onset was associated with enlargement of lateral ventricles (p = .001) and greater whole brain (p = .003), white matter (p < .001), corpus callosum (p < .001), and thalamus (p = .003) volume loss over 48 months. Higher QAlb was associated with higher Expanded Disability Status Scale score over 48 months (p = .002). CONCLUSIONS: Increased QAlb at clinical onset is associated with increased brain atrophy and greater disability in patients after first clinical event suggestive of MS.
BACKGROUND: The utility of blood-brain barrier (BBB) biomarkers for clinical and magnetic resonance imaging progression in multiple sclerosis (MS) has not been extensively investigated. OBJECTIVES: To determine whether cerebrospinal fluid (CSF) measures of BBB at clinical onset predict radiological and clinical deterioration over 48 months. METHODS: This longitudinal study included 182 patients after first clinical event suggestive of MS treated with weekly intramuscular interferon beta-1a. CSF and serum samples were analyzed for leukocytes, total protein, albumin, immunoglobulins, and oligoclonal bands. Optimal thresholds for the albumin quotient (QAlb) were determined. Mixed-effect model analyses, adjusted for age, gender, and treatment escalation, were used to analyze relationship between CSF measures and disease activity outcomes over 48 months of follow-up. RESULTS: Increased QAlb at clinical onset was associated with enlargement of lateral ventricles (p = .001) and greater whole brain (p = .003), white matter (p < .001), corpus callosum (p < .001), and thalamus (p = .003) volume loss over 48 months. Higher QAlb was associated with higher Expanded Disability Status Scale score over 48 months (p = .002). CONCLUSIONS: Increased QAlb at clinical onset is associated with increased brain atrophy and greater disability in patients after first clinical event suggestive of MS.
Authors: Kelly Fellows; Tomas Uher; Richard W Browne; Bianca Weinstock-Guttman; Dana Horakova; Helena Posova; Manuela Vaneckova; Zdenek Seidl; Jan Krasensky; Michaela Tyblova; Eva Havrdova; Robert Zivadinov; Murali Ramanathan Journal: J Lipid Res Date: 2015-08-04 Impact factor: 5.922
Authors: Vinzenz Fleischer; Gabriel Gonzalez-Escamilla; Dumitru Ciolac; Philipp Albrecht; Patrick Küry; Joel Gruchot; Michael Dietrich; Christina Hecker; Thomas Müntefering; Stefanie Bock; Mohammadsaleh Oshaghi; Angela Radetz; Manuela Cerina; Julia Krämer; Lydia Wachsmuth; Cornelius Faber; Hans Lassmann; Tobias Ruck; Sven G Meuth; Muthuraman Muthuraman; Sergiu Groppa Journal: Proc Natl Acad Sci U S A Date: 2021-09-07 Impact factor: 11.205
Authors: Christopher C Hemond; Brian C Healy; Shahamat Tauhid; Maria A Mazzola; Francisco J Quintana; Roopali Gandhi; Howard L Weiner; Rohit Bakshi Journal: Neurol Neuroimmunol Neuroinflamm Date: 2019-02-14