Contributions
Abstract: P536
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction and aim: Cognitive impairment (CI) is a common and disabling symptom of multiple sclerosis (MS), but its pathogenesis is controversial and there is no effective treatment. White and grey matter damage has been proposed as one of the possible causes of MS-related CI and the disruption of white matter neuronal pathways may contribute to the impairment of specific cognitive domains, such as information processing speed. Since cerebrospinal fluid (CSF) neurofilament light chain (NfL) is a reliable marker of neuroaxonal damage, the aim of our work was to examine the relationship between CSF NfL and cognitive performance in MS patients.
Patients and methods: We enrolled 28 consecutive newly diagnosed MS patients (mean age 39.1 ± 11.3 years, F/M =2.5). All of them underwent CSF analysis as part of the usual diagnostic work-up. CSF NfL was measured by means of a newly developed in-house ELISA. Neuropsychological evaluation with the Rao's Brief Repeatable Battery (BRB) was performed at the time of CSF collection (mean time between lumbar puncture and BRB execution: 25.5 ± 19.2 days). Normative values adjusted according to gender and education for Italian population were used. The presence of specific cognitive domains impairment was defined by the failure of ≥1 test exploring that domain.
Results: CSF NfL was higher in patients with global CI as defined by the presence of impairment in ≥2 cognitive domains explored by the BRB (947.8±400.7 vs 518.4±424.7 pg/mL, p< 0.01). Specifically, CSF NfL was higher in patients with impairment in the information processing speed (820.8±413.6 vs 513.6±461.4 pg/mL, p< 0.05) and verbal fluency (1292±511 vs 582.8±395.4 pg/mL, p< 0.05) tests. Finally, CSF NfL concentration was inversely correlated with the scores of the following BRB tests: SRT-LTS (r=-0.45, p< 0.05), SRT-DR (r=-0.52, p< 0.01) for verbal memory, SPART-IR (r=-0.49, p< 0.01) for visuospatial memory, SDMT (r=-0.45, p< 0.05), PASAT-3 (r=-0.57, p< 0.01) and PASAT-2 (r=-0.54, p< 0.01) for information processing speed.
Conclusions: CSF NfL concentration may reflect CI in MS patients and has a stronger negative association with information processing speed tests scores. However, CSF NfL seems to reflect also the performance in other cognitive domains during MS, such as verbal memory, visuospatial memory and verbal fluency. Degeneration of larger myelinated axons, as reflected by CSF NfL, may therefore be an important determinant of CI in MS patients.
Disclosure: Gaetani Lorenzo received travel grants from Biogen, Novartis, Teva, Genzyme and Almirall to attend conferences. Salvadori Nicola: nothing to disclose. Viviana Lisetti: nothing to disclose. Eusebi Paolo: nothing to disclose. Mancini Andrea: nothing to disclose. Gentili Lucia: nothing to disclose. Germano Francesca: nothing to disclose. Sarchielli Paola: nothing to disclose. Calabresi Paolo received/receive research support from Bayer Schering, Biogen-Dompé, Boehringer Ingelheim, Eisai, Lundbeck, Merck-Serono, Novartis, Sanofi-Aventis, Sigma-Tau, and UCB Pharma. He also receives/received support from Ricerca Corrente IRCCS, Ricerca Finalizzata IRCCS, European Community Grant REPLACES (restorative plasticity at corticostriatal excitatory synapses), the Italian Minister of Health, and AIFA (Agenzia Italiana del Farmaco). Blennow Kaj has served as a consultant or at advisory boards for Alzheon, BioArctic, Biogen, Eli Lilly, Fujirebio Europe, IBL International, Pfizer, and Roche Diagnostics, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg. Parnetti Lucilla: nothing to disclose. Zetterberg Henrik is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg. Di Filippo Massimiliano participated to advisory boards of Biogen Idec, Teva and Bayer, received travel grants from Bayer Schering, Biogen-Dompé, Biogen-Idec, Merck-Serono, Novartis and Sanofi-Aventis to attend national and international conferences and speaker and writing honoraria from Biogen Idec, Novartis and Sanofi-Genzyme.
Abstract: P536
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction and aim: Cognitive impairment (CI) is a common and disabling symptom of multiple sclerosis (MS), but its pathogenesis is controversial and there is no effective treatment. White and grey matter damage has been proposed as one of the possible causes of MS-related CI and the disruption of white matter neuronal pathways may contribute to the impairment of specific cognitive domains, such as information processing speed. Since cerebrospinal fluid (CSF) neurofilament light chain (NfL) is a reliable marker of neuroaxonal damage, the aim of our work was to examine the relationship between CSF NfL and cognitive performance in MS patients.
Patients and methods: We enrolled 28 consecutive newly diagnosed MS patients (mean age 39.1 ± 11.3 years, F/M =2.5). All of them underwent CSF analysis as part of the usual diagnostic work-up. CSF NfL was measured by means of a newly developed in-house ELISA. Neuropsychological evaluation with the Rao's Brief Repeatable Battery (BRB) was performed at the time of CSF collection (mean time between lumbar puncture and BRB execution: 25.5 ± 19.2 days). Normative values adjusted according to gender and education for Italian population were used. The presence of specific cognitive domains impairment was defined by the failure of ≥1 test exploring that domain.
Results: CSF NfL was higher in patients with global CI as defined by the presence of impairment in ≥2 cognitive domains explored by the BRB (947.8±400.7 vs 518.4±424.7 pg/mL, p< 0.01). Specifically, CSF NfL was higher in patients with impairment in the information processing speed (820.8±413.6 vs 513.6±461.4 pg/mL, p< 0.05) and verbal fluency (1292±511 vs 582.8±395.4 pg/mL, p< 0.05) tests. Finally, CSF NfL concentration was inversely correlated with the scores of the following BRB tests: SRT-LTS (r=-0.45, p< 0.05), SRT-DR (r=-0.52, p< 0.01) for verbal memory, SPART-IR (r=-0.49, p< 0.01) for visuospatial memory, SDMT (r=-0.45, p< 0.05), PASAT-3 (r=-0.57, p< 0.01) and PASAT-2 (r=-0.54, p< 0.01) for information processing speed.
Conclusions: CSF NfL concentration may reflect CI in MS patients and has a stronger negative association with information processing speed tests scores. However, CSF NfL seems to reflect also the performance in other cognitive domains during MS, such as verbal memory, visuospatial memory and verbal fluency. Degeneration of larger myelinated axons, as reflected by CSF NfL, may therefore be an important determinant of CI in MS patients.
Disclosure: Gaetani Lorenzo received travel grants from Biogen, Novartis, Teva, Genzyme and Almirall to attend conferences. Salvadori Nicola: nothing to disclose. Viviana Lisetti: nothing to disclose. Eusebi Paolo: nothing to disclose. Mancini Andrea: nothing to disclose. Gentili Lucia: nothing to disclose. Germano Francesca: nothing to disclose. Sarchielli Paola: nothing to disclose. Calabresi Paolo received/receive research support from Bayer Schering, Biogen-Dompé, Boehringer Ingelheim, Eisai, Lundbeck, Merck-Serono, Novartis, Sanofi-Aventis, Sigma-Tau, and UCB Pharma. He also receives/received support from Ricerca Corrente IRCCS, Ricerca Finalizzata IRCCS, European Community Grant REPLACES (restorative plasticity at corticostriatal excitatory synapses), the Italian Minister of Health, and AIFA (Agenzia Italiana del Farmaco). Blennow Kaj has served as a consultant or at advisory boards for Alzheon, BioArctic, Biogen, Eli Lilly, Fujirebio Europe, IBL International, Pfizer, and Roche Diagnostics, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg. Parnetti Lucilla: nothing to disclose. Zetterberg Henrik is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg. Di Filippo Massimiliano participated to advisory boards of Biogen Idec, Teva and Bayer, received travel grants from Bayer Schering, Biogen-Dompé, Biogen-Idec, Merck-Serono, Novartis and Sanofi-Aventis to attend national and international conferences and speaker and writing honoraria from Biogen Idec, Novartis and Sanofi-Genzyme.