Objective Pathological studies established that irreversible neurological disability in multiple sclerosis (MS) is associated with axonal and neuronal injury which can be detected by advanced cerebrospinal fluid (CSF) analysis and MRI techniques. However, the link between the two approaches and the advantage of combining them have not been explored in detail. This cross-sectional study is aimed at examining the correlation between CSF-detected neurodegeneration and MRI gray matter involvement in MS. Materials and Methods Starting from December 2011, consecutive patients with clinically isolated syndrome (CIS) or MS, diagnosed according to 2010 McDonald's criteria and with a CSF sample stored at Verona University Hospital Laboratory of Neuropathology have been considered eligible for the study. Enrolled subjects underwent CSF analysis, including ELISA to determine neurofilament light chain (NFL) concentration, and brain MRI, including volumetric T1-weighted, Fast Fluid Attenuated Inversion Recovery (FLAIR), and Double Inversion Recovery (DIR) sequences. All patients had a baseline neurological examination to estimate expanded disability status scale (EDSS) score. The correlation between CSF NFL concentration and MRI markers of gray matter pathology was analyzed as well as the association between these variables and neurological disability. Results As of May 2014, 40 eligible patients have been identified of which 25 have completed CSF analysis and MRI protocol. The study group is made of 17 females and 8 males with median age at inclusion of 31.5 (16.7-59.5) years. Three subjects have a CIS, 20 relapsing-remitting and 2 primary progressive MS with a median interval between clinical onset and study entry of 4.9 (0.1-379.5) months. Median EDSS score at CSF collection was 2.0 (0-4.0). Median CSF NFL concentration was 3304 (808-15000) ng/l and it did not change significantly according to sex, age, clinical course, disease duration and EDSS score. All patients had dissemination of lesions in space on MRI, while 8 subjects (32%) had one or more cortical lesions on DIR images. Median NFL concentration was 2854 (808-9973) ng/l in CSF of patients with evidence of cortical involvement and 3718 (1120-15000) ng/l in CSF of cases with no cortical lesions (p=0.6). Discussion and Conclusions In the present series, patients with MS and CIS had CSF NFL concentration well above the normal upper limit reported by previous studies. Based on preliminary results, NFL levels appear to be similar in the CSF of MS cases with and without cortical lesions detected on MRI. Further research on a larger sample and with additional measures is warranted.
Correlation between cerebrospinal fluid markers of neurodegeneration and MRI measures of gray matter pathology in multiple sclerosis
GAJOFATTO, Alberto;BONGIANNI, Matilde;CALABRESE, Massimiliano;TURATTI, Marco;MONACO, Salvatore;BENEDETTI, MARIADONATA
2014-01-01
Abstract
Objective Pathological studies established that irreversible neurological disability in multiple sclerosis (MS) is associated with axonal and neuronal injury which can be detected by advanced cerebrospinal fluid (CSF) analysis and MRI techniques. However, the link between the two approaches and the advantage of combining them have not been explored in detail. This cross-sectional study is aimed at examining the correlation between CSF-detected neurodegeneration and MRI gray matter involvement in MS. Materials and Methods Starting from December 2011, consecutive patients with clinically isolated syndrome (CIS) or MS, diagnosed according to 2010 McDonald's criteria and with a CSF sample stored at Verona University Hospital Laboratory of Neuropathology have been considered eligible for the study. Enrolled subjects underwent CSF analysis, including ELISA to determine neurofilament light chain (NFL) concentration, and brain MRI, including volumetric T1-weighted, Fast Fluid Attenuated Inversion Recovery (FLAIR), and Double Inversion Recovery (DIR) sequences. All patients had a baseline neurological examination to estimate expanded disability status scale (EDSS) score. The correlation between CSF NFL concentration and MRI markers of gray matter pathology was analyzed as well as the association between these variables and neurological disability. Results As of May 2014, 40 eligible patients have been identified of which 25 have completed CSF analysis and MRI protocol. The study group is made of 17 females and 8 males with median age at inclusion of 31.5 (16.7-59.5) years. Three subjects have a CIS, 20 relapsing-remitting and 2 primary progressive MS with a median interval between clinical onset and study entry of 4.9 (0.1-379.5) months. Median EDSS score at CSF collection was 2.0 (0-4.0). Median CSF NFL concentration was 3304 (808-15000) ng/l and it did not change significantly according to sex, age, clinical course, disease duration and EDSS score. All patients had dissemination of lesions in space on MRI, while 8 subjects (32%) had one or more cortical lesions on DIR images. Median NFL concentration was 2854 (808-9973) ng/l in CSF of patients with evidence of cortical involvement and 3718 (1120-15000) ng/l in CSF of cases with no cortical lesions (p=0.6). Discussion and Conclusions In the present series, patients with MS and CIS had CSF NFL concentration well above the normal upper limit reported by previous studies. Based on preliminary results, NFL levels appear to be similar in the CSF of MS cases with and without cortical lesions detected on MRI. Further research on a larger sample and with additional measures is warranted.
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