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Published in: BMC Neurology 1/2018

Open Access 01-12-2018 | Research article

A cross-sectional and longitudinal study evaluating brain volumes, RNFL, and cognitive functions in MS patients and healthy controls

Authors: Jessica Frau, Giuseppe Fenu, Alessio Signori, Giancarlo Coghe, Lorena Lorefice, Maria Antonietta Barracciu, Vincenzo Sechi, Federico Cabras, Mauro Badas, Maria Giovanna Marrosu, Eleonora Cocco

Published in: BMC Neurology | Issue 1/2018

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Abstract

Background

The principal biomarker of neurodegeneration in multiple sclerosis (MS) is believed to be brain volume, which is associated with cognitive functions and retinal nerve fibre layer (RNFL). A cross-sectional and longitudinal assessment of the relationship between RNFL, cognitive functions and brain volume.

Methods

At baseline, relapsing patients and healthy controls underwent 1.5 T MRI to estimate the normalized volume of brain (NBV), grey (NGV), white (NWV) and peripheral grey (pNGV) matter. Cognitive functions were evaluated by BICAMS, RNFL by Spectral-Domain OCT. Patients were re-evaluated after 12 months.

Results

Cognitive functions, brain volume, and RNFL differed between the group of 66 patients and that of 16 healthy controls. In the MS group, at baseline, an association was found between: p-NGV and symbol-digit (SDMT) (p = 0.022); temporal-RNFL and NBV (p = 0.007), NWV (p = 0.012), NGV (p = 0.048), and p-NGV (p = 0.021); papillo-macular bundle-RNFL and NBV (p = 0.013), NWV (p = 0.02), NGV (p = 0.049), and p-NGV (p = 0.032). Over the observational period, we found a reduction of brain volume (p < 0.001), average-RNFL (p = 0.001), temporal-RNFL (p = 0.006), and papillo-macular bundle-RNFL (p = 0.009). No association was found between OCT, MRI, and cognitive changes.

Conclusions

Brain volume, cognitive functions, and RNFL are continuous measures of different neurodegenerative aspects. BICAMS and OCT have low costs and can be easily used in clinical practice to monitor neurodegeneration.
Literature
1.
go back to reference Kamm CP, Uitdehaag BM, Polman CH. Multiple sclerosis: current knowledge and future outlook. Eur Neurol. 2014;72(3-4):132–41.CrossRefPubMed Kamm CP, Uitdehaag BM, Polman CH. Multiple sclerosis: current knowledge and future outlook. Eur Neurol. 2014;72(3-4):132–41.CrossRefPubMed
2.
go back to reference Río J, Rovira À, Tintoré M, Otero-Romero S, et al. Disability progression markers over 6-12 years in interferon-β-treated multiple sclerosis patients. Mult Scler. 2017;1:1352458517698052. Río J, Rovira À, Tintoré M, Otero-Romero S, et al. Disability progression markers over 6-12 years in interferon-β-treated multiple sclerosis patients. Mult Scler. 2017;1:1352458517698052.
3.
go back to reference Sastre-Garriga J, Pareto D, Rovira À. Brain atrophy in multiple sclerosis: clinical relevance and technical aspects. Neuroimaging Clin N Am. 2017;27(2):289–300.CrossRefPubMed Sastre-Garriga J, Pareto D, Rovira À. Brain atrophy in multiple sclerosis: clinical relevance and technical aspects. Neuroimaging Clin N Am. 2017;27(2):289–300.CrossRefPubMed
4.
go back to reference De Stefano N, Airas L, Grigoriadis N, et al. Clinical relevance of brain volume measures in multiple sclerosis. CNS Drugs. 2014;28(2):147–56.CrossRefPubMed De Stefano N, Airas L, Grigoriadis N, et al. Clinical relevance of brain volume measures in multiple sclerosis. CNS Drugs. 2014;28(2):147–56.CrossRefPubMed
5.
go back to reference Rocca MA, Amato MP, De Stefano N, et al. Clinical and imaging assessment of cognitive dysfunction in multiple sclerosis. Lancet Neurol. 2015;14(3):302–17.CrossRefPubMed Rocca MA, Amato MP, De Stefano N, et al. Clinical and imaging assessment of cognitive dysfunction in multiple sclerosis. Lancet Neurol. 2015;14(3):302–17.CrossRefPubMed
6.
go back to reference Chiaravalloti ND, DeLuca J. Cognitive impairment in multiple sclerosis. Lancet Neurol. 2008;7(12):1139–51.CrossRefPubMed Chiaravalloti ND, DeLuca J. Cognitive impairment in multiple sclerosis. Lancet Neurol. 2008;7(12):1139–51.CrossRefPubMed
7.
go back to reference Ruano L, Portaccio E, Goretti B, et al. Age and disability drive cognitive impairment in multiple sclerosis across disease subtypes. Mult Scler. 2017;23(9):1258–67.CrossRefPubMed Ruano L, Portaccio E, Goretti B, et al. Age and disability drive cognitive impairment in multiple sclerosis across disease subtypes. Mult Scler. 2017;23(9):1258–67.CrossRefPubMed
9.
go back to reference Parisi V, Manni G, Spadaro M, et al. Correlation between morphological and functional retinal impairment in multiple sclerosis patients. Invest Ophthalmol Vis Sci. 1999;40(11):2520–7.PubMed Parisi V, Manni G, Spadaro M, et al. Correlation between morphological and functional retinal impairment in multiple sclerosis patients. Invest Ophthalmol Vis Sci. 1999;40(11):2520–7.PubMed
10.
go back to reference Gordon-Lipkin E, Chodkowski B, Reich DS, et al. Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis. Neurology. 2007;69(16):1603–9.CrossRefPubMed Gordon-Lipkin E, Chodkowski B, Reich DS, et al. Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis. Neurology. 2007;69(16):1603–9.CrossRefPubMed
11.
go back to reference Sepulcre J, Murie-Fernandez M, Salinas-Alaman A, et al. Diagnostic accuracy of retinal abnormalities in predicting disease activity in MS. Neurology. 2007;68(18):1488–94.CrossRefPubMed Sepulcre J, Murie-Fernandez M, Salinas-Alaman A, et al. Diagnostic accuracy of retinal abnormalities in predicting disease activity in MS. Neurology. 2007;68(18):1488–94.CrossRefPubMed
12.
go back to reference Grazioli E, Zivadinov R, Weinstock-Guttman B, et al. Retinal nerve fiber layer thickness is associated with brain MRI outcomes in multiple sclerosis. J Neurol Sci. 2008;268(1-2):12–7.CrossRefPubMed Grazioli E, Zivadinov R, Weinstock-Guttman B, et al. Retinal nerve fiber layer thickness is associated with brain MRI outcomes in multiple sclerosis. J Neurol Sci. 2008;268(1-2):12–7.CrossRefPubMed
13.
go back to reference Siger M, Dziegielewski K, Jasek L, et al. Optical coherence tomography in multiple sclerosis: thickness of the retinal nerve fiber layer as a potential measure of axonal loss and brain atrophy. J Neurol. 2008;255(10):1555–60.CrossRefPubMed Siger M, Dziegielewski K, Jasek L, et al. Optical coherence tomography in multiple sclerosis: thickness of the retinal nerve fiber layer as a potential measure of axonal loss and brain atrophy. J Neurol. 2008;255(10):1555–60.CrossRefPubMed
14.
15.
go back to reference Lamirel C, Newman NJ, Biousse V. Optical coherence tomography (OCT) in optic neuritis and multiple sclerosis. Rev Neurol (Paris). 2010;166(12):978–86.CrossRef Lamirel C, Newman NJ, Biousse V. Optical coherence tomography (OCT) in optic neuritis and multiple sclerosis. Rev Neurol (Paris). 2010;166(12):978–86.CrossRef
16.
go back to reference Lange AP, Sadjadi R, Saeedi J, et al. Time-domain and spectral-domain optical coherence tomography of retinal nerve Fiber layer in MS patients and healthy controls. J Ophthalmol. 2012;2012:564627.CrossRefPubMedPubMedCentral Lange AP, Sadjadi R, Saeedi J, et al. Time-domain and spectral-domain optical coherence tomography of retinal nerve Fiber layer in MS patients and healthy controls. J Ophthalmol. 2012;2012:564627.CrossRefPubMedPubMedCentral
17.
go back to reference Knight OJ, Chang RT, Feuer WJ, et al. Comparison of retinal nerve fiber layer measurements using time domain and spectral domain optical coherent tomography. Ophthalmology. 2009;116(7):1271–7.CrossRefPubMedPubMedCentral Knight OJ, Chang RT, Feuer WJ, et al. Comparison of retinal nerve fiber layer measurements using time domain and spectral domain optical coherent tomography. Ophthalmology. 2009;116(7):1271–7.CrossRefPubMedPubMedCentral
18.
go back to reference Watson GM, Keltner JL, Chin EK, et al. Comparison of retinal nerve fiber layer and central macular thickness measurements among five different optical coherence tomography instruments in patients with multiple sclerosis and optic neuritis. J Neuro-Oncol. 2011;31(2):110–6. Watson GM, Keltner JL, Chin EK, et al. Comparison of retinal nerve fiber layer and central macular thickness measurements among five different optical coherence tomography instruments in patients with multiple sclerosis and optic neuritis. J Neuro-Oncol. 2011;31(2):110–6.
19.
go back to reference Arthur SN, Smith SD, Wright MM, et al. Reproducibility and agreement in evaluating retinal nerve fibre layer thickness between stratus and Spectralis OCT. Eye (Lond). 2011;25(2):192–200.CrossRef Arthur SN, Smith SD, Wright MM, et al. Reproducibility and agreement in evaluating retinal nerve fibre layer thickness between stratus and Spectralis OCT. Eye (Lond). 2011;25(2):192–200.CrossRef
20.
go back to reference Goretti B, Niccolai C, Hakiki B, et al. The brief international cognitive assessment for multiple sclerosis (BICAMS): normative values with gender, age and education corrections in the Italian population. BMC Neurol. 2014;14:171.CrossRefPubMedPubMedCentral Goretti B, Niccolai C, Hakiki B, et al. The brief international cognitive assessment for multiple sclerosis (BICAMS): normative values with gender, age and education corrections in the Italian population. BMC Neurol. 2014;14:171.CrossRefPubMedPubMedCentral
21.
go back to reference Smith SM, Zhang Y, Jenkinson M, et al. Accurate, robust, and automated longitudinal and cross-sectional brain change analysis. NeuroImage. 2002;17(1):479–89.CrossRefPubMed Smith SM, Zhang Y, Jenkinson M, et al. Accurate, robust, and automated longitudinal and cross-sectional brain change analysis. NeuroImage. 2002;17(1):479–89.CrossRefPubMed
22.
go back to reference Battaglini M, Jenkinson M, De Stefano N. Evaluating and reducing the impact of white matter lesions on brain volume measurements. Hum Brain Mapp. 2012;33(9):2062–71.CrossRefPubMed Battaglini M, Jenkinson M, De Stefano N. Evaluating and reducing the impact of white matter lesions on brain volume measurements. Hum Brain Mapp. 2012;33(9):2062–71.CrossRefPubMed
23.
go back to reference Martinez-Lapiscina EH, Arnow S, Wilson JA, et al. Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study. Lancet Neurol. 2016;15(6):574–84.CrossRefPubMed Martinez-Lapiscina EH, Arnow S, Wilson JA, et al. Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study. Lancet Neurol. 2016;15(6):574–84.CrossRefPubMed
24.
go back to reference Young KL, Brandt AU, Petzold A, et al. Loss of retinal nerve fibre layer axons indicates white but not grey matter damage in early multiple sclerosis. Eur J Nurol. 2013;20(5):803–11.CrossRef Young KL, Brandt AU, Petzold A, et al. Loss of retinal nerve fibre layer axons indicates white but not grey matter damage in early multiple sclerosis. Eur J Nurol. 2013;20(5):803–11.CrossRef
25.
go back to reference Toledo J, Sepulcre J, Salinas-Alaman A, et al. Retinal nerve fiber layer atrophy is associated with physical and cognitive disability in multiple sclerosis. Mult Scler. 2008;14(7):906–12.CrossRefPubMed Toledo J, Sepulcre J, Salinas-Alaman A, et al. Retinal nerve fiber layer atrophy is associated with physical and cognitive disability in multiple sclerosis. Mult Scler. 2008;14(7):906–12.CrossRefPubMed
26.
go back to reference Peterson JW, Bö L, Mörk S, Chang A, et al. Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol. 2001;50(3):389–400.CrossRefPubMed Peterson JW, Bö L, Mörk S, Chang A, et al. Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol. 2001;50(3):389–400.CrossRefPubMed
27.
go back to reference Benedict RH, Shucard JL, Zivadinov R, et al. Neuropsychological impairment in systemic lupus erythematosus: a comparison with multiple sclerosis. Neuropsychol Rev. 2008;18(2):149–66.CrossRefPubMedPubMedCentral Benedict RH, Shucard JL, Zivadinov R, et al. Neuropsychological impairment in systemic lupus erythematosus: a comparison with multiple sclerosis. Neuropsychol Rev. 2008;18(2):149–66.CrossRefPubMedPubMedCentral
Metadata
Title
A cross-sectional and longitudinal study evaluating brain volumes, RNFL, and cognitive functions in MS patients and healthy controls
Authors
Jessica Frau
Giuseppe Fenu
Alessio Signori
Giancarlo Coghe
Lorena Lorefice
Maria Antonietta Barracciu
Vincenzo Sechi
Federico Cabras
Mauro Badas
Maria Giovanna Marrosu
Eleonora Cocco
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2018
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-018-1065-9

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