Mario Stampanoni Bassi1,2, Ennio Iezzi1, Doriana Landi2, Fabrizia Monteleone2, Luana Gilio1,2, Ilaria Simonelli3, Alessandra Musella4, Georgia Mandolesi4, Francesca De Vito4, Roberto Furlan5, Annamaria Finardi5, Girolama A Marfia1,2, Diego Centonze6,7, Fabio Buttari1. 1. Unit of Neurology and Neurorehabilitation, IRCCS Neuromed, Via Atinense 18, 86077, Pozzilli, IS, Italy. 2. Multiple Sclerosis Research Unit, Department of Systems Medicine, Tor Vergata University, Via Montpellier 1, 00133, Rome, Italy. 3. Service of Medical Statistics and Information Technology, Fatebenefratelli Foundation for Health Research and Education, Rome, Italy. 4. Laboratory of Neuroimmunology and Synaptic Plasticity, IRCCS San Raffaele Pisana, Via di Val Cannuta 247, 00163, Rome, Italy. 5. Neuroimmunology Unit, Division of Neuroscience, Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute, Milan, Italy. 6. Unit of Neurology and Neurorehabilitation, IRCCS Neuromed, Via Atinense 18, 86077, Pozzilli, IS, Italy. centonze@uniroma2.i. 7. Multiple Sclerosis Research Unit, Department of Systems Medicine, Tor Vergata University, Via Montpellier 1, 00133, Rome, Italy. centonze@uniroma2.i.
Abstract
BACKGROUND: Clinical deterioration of relapsing-remitting MS (RR-MS) patients reflects not only the number and severity of overt inflammatory and demyelinating episodes, but also subtle central damage caused by persistent exposure to inflammatory molecules. OBJECTIVE: To explore the correlation between levels of CSF inflammatory molecules at the time of diagnosis and both demographic and clinical characteristics of a large sample of RR-MS patients, as well as the predictive value of cytokine levels on their prospective disease course. METHODS: In 205 patients diagnosed with RR-MS, we measured at the time of diagnosis the CSF levels of inflammatory molecules. Clinical and MRI evaluation was collected at the time of CSF withdrawal and during a median follow-up of 3 years. RESULTS: The time interval between the first anamnestic episode of focal neurological dysfunction and RR-MS diagnosis was the main factor associated with high CSF levels of IL-6 and IL-8. Furthermore, elevated CSF levels of these cytokines correlated with enhanced risk of clinical and radiological disease reactivation, switch to second-line treatments, and with disability progression in the follow-up. CONCLUSIONS: Delayed diagnosis and treatment initiation are associated with higher CSF levels of IL-6 and IL-8 in RR-MS, leading to worsening disease course and poor response to treatments.
BACKGROUND: Clinical deterioration of relapsing-remitting MS (RR-MS) patients reflects not only the number and severity of overt inflammatory and demyelinating episodes, but also subtle central damage caused by persistent exposure to inflammatory molecules. OBJECTIVE: To explore the correlation between levels of CSF inflammatory molecules at the time of diagnosis and both demographic and clinical characteristics of a large sample of RR-MS patients, as well as the predictive value of cytokine levels on their prospective disease course. METHODS: In 205 patients diagnosed with RR-MS, we measured at the time of diagnosis the CSF levels of inflammatory molecules. Clinical and MRI evaluation was collected at the time of CSF withdrawal and during a median follow-up of 3 years. RESULTS: The time interval between the first anamnestic episode of focal neurological dysfunction and RR-MS diagnosis was the main factor associated with high CSF levels of IL-6 and IL-8. Furthermore, elevated CSF levels of these cytokines correlated with enhanced risk of clinical and radiological disease reactivation, switch to second-line treatments, and with disability progression in the follow-up. CONCLUSIONS: Delayed diagnosis and treatment initiation are associated with higher CSF levels of IL-6 and IL-8 in RR-MS, leading to worsening disease course and poor response to treatments.
Authors: L D Jacobs; R W Beck; J H Simon; R P Kinkel; C M Brownscheidle; T J Murray; N A Simonian; P J Slasor; A W Sandrock Journal: N Engl J Med Date: 2000-09-28 Impact factor: 91.245
Authors: Z Stelmasiak; M Kozioł-Montewka; B Dobosz; K Rejdak; H Bartosik-Psujek; K Mitosek-Szewczyk; E Belniak-Legieć Journal: Med Sci Monit Date: 2000 Nov-Dec
Authors: Ludwig Kappos; Gilles Edan; Mark S Freedman; Xavier Montalbán; Hans-Peter Hartung; Bernhard Hemmer; Edward J Fox; Frederik Barkhof; Sven Schippling; Andrea Schulze; Dirk Pleimes; Christoph Pohl; Rupert Sandbrink; Gustavo Suarez; Eva-Maria Wicklein Journal: Neurology Date: 2016-08-10 Impact factor: 9.910
Authors: Marko Petržalka; Eva Meluzínová; Jana Libertínová; Hana Mojžišová; Jitka Hanzalová; Petra Ročková; Martin Elišák; Silvia Kmetonyová; Jan Šanda; Ondřej Sobek; Petr Marusič Journal: PLoS One Date: 2022-06-27 Impact factor: 3.752