Structural brain abnormalities are related to retinal nerve fiber layer thinning and disease duration in neuromyelitis optica spectrum disorders

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOBackground: Although aquaporin-4 (AQP4) is widely expressed in the human brain cortex, lesions are rare in neuromyelitis optica (NMO) spectrum disorders (NMOSD). Recently, however, several studies have demonstrated occult structural brain atrophy in NMO. Objective: This study aims to investigate magnetic resonance imaging (MRI) patterns of gray matter (GM) and white matter (WM) abnormalities in patients with NMOSD and to assess the visual pathway integrity during disease duration correlation of the retinal nerve fiber layer (RNFL) and pericalcarine cortex thickness. Methods: Twenty-one patients with NMOSD and 34 matched healthy controls underwent both high-field MRI (3T) high-resolution T1-weighted and diffusion-tensor MRI. Voxel-based morphometry, cortical analyses (Freesurfer) and diffusion-tensor imaging (DTI) analyses (TBSS-FSL) were used to investigate brain abnormalities. In addition, RNFL measurement by optic-coherence tomography (OCT) was performed. Results: We demonstrate that NMOSD is associated with GM and WM atrophy, encompassing more frequently the motor, sensory and visual pathways, and that the extent of GM atrophy correlates with disease duration. Furthermore, we demonstrate for the first time a correlation between RNFL and pericalcarine cortical thickness, with cortical atrophy evolving over the course of disease. Conclusions: Our findings indicate a role for retrograde and anterograde neurodegeneration in GM atrophy in NMOSD. However, the presence atrophy encompassing almost all lobes suggests that additional pathomechanisms might also be involved. © The Author(s) 2014 Reprints and permissions:.Background: Although aquaporin-4 (AQP4) is widely expressed in the human brain cortex, lesions are rare in neuromyelitis optica (NMO) spectrum disorders (NMOSD). Recently, however, several studies have demonstrated occult structural brain atrophy in NMO. Objective: This study aims to investigate magnetic resonance imaging (MRI) patterns of gray matter (GM) and white matter (WM) abnormalities in patients with NMOSD and to assess the visual pathway integrity during disease duration correlation of the retinal nerve fiber layer (RNFL) and pericalcarine cortex thickness. Methods: Twenty-one patients with NMOSD and 34 matched healthy controls underwent both high-field MRI (3T) high-resolution T1-weighted and diffusion-tensor MRI. Voxel-based morphometry, cortical analyses (Freesurfer) and diffusion-tensor imaging (DTI) analyses (TBSS-FSL) were used to investigate brain abnormalities. In addition, RNFL measurement by optic-coherence tomography (OCT) was performed. Results: We demonstrate that NMOSD is associated with GM and WM atrophy, encompassing more frequently the motor, sensory and visual pathways, and that the extent of GM atrophy correlates with disease duration. Furthermore, we demonstrate for the first time a correlation between RNFL and pericalcarine cortical thickness, with cortical atrophy evolving over the course of disease. Conclusions: Our findings indicate a role for retrograde and anterograde neurodegeneration in GM atrophy in NMOSD. However, the presence atrophy encompassing almost all lobes suggests that additional pathomechanisms might also be involved.20911891197FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO09/514256 ; 11/18728-5; 12/04565-0Sem informaçãoSem informaçãoWingerchuk, D.M., Hogancamp, W.F., O'Brien, P.C., Weinshenker, B.G., The clinical course of neuromyelitis optica (Devic's syndrome) (1999) Neurology, 53 (5), pp. 1107-1114Jarius, S., Ruprecht, K., Wildemann, B., Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients (2012) J Neuroinflammation, 9, p. 14Lennon, P.V.A., Wingerchuk, D.M., Kryzer, T.J., Pittock, S.J., Lucchinetti, C.F., Fujihara, K., Nakashima, I., Weinshenker, B.G., A serum autoantibody marker of neuromyelitis optica: Distinction from multiple sclerosis (2004) Lancet, 364 (9451), pp. 2106-2112. , DOI 10.1016/S0140-6736(04)17551-X, PII S014067360417551XJarius, S., Wildemann, B., AQP4 antibodies in neuromyelitis optica: Diagnostic and pathogenetic relevance (2010) Nat Rev Neurol, 6, pp. 383-392Akman-Demir, G., Tüzün, E., Waters, P., Prognostic implications of aquaporin-4 antibody status in neuromyelitis optica patients (2011) J Neurol, 258, pp. 464-470Weinshenker, B.G., Wingerchuk, D.M., Vukusic, S., Linbo, L., Pittock, S.J., Lucchinetti, C.F., Lennon, V.A., Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis (2006) Annals of Neurology, 59 (3), pp. 566-569. , DOI 10.1002/ana.20770Jarius, S., Frederikson, J., Waters, P., Frequency and prognostic impact of antibodies to aquaporin-4 in patients with optic neuritis (2010) J Neurol Sci, 298, pp. 158-162Petzold, A., Pittock, S., Lennon, V., Neuromyelitis optica-IgG (aquaporin-4) autoantibodies in immune mediated optic neuritis (2010) J Neurol Neurosurg Psychiatry, 81, pp. 109-111Wingerchuk, D.M., Diagnosis and treatment of neuromyelitis optica (2007) Neurologist, 13 (1), pp. 2-11. , DOI 10.1097/01.nrl.0000250927.21903.f8, PII 0012789320070100000002Popescu, B.F., Parisi, J.E., Cabrera-Gómez, J.A., Absence of cortical demyelination in neuromyelitis optica (2010) Neurology, 75, pp. 2103-2109Calabrese, M., Oh, M.S., Favaretto, A., No MRI evidence of cortical lesions in neuromyelitis optica (2012) Neurology, 79, pp. 1671-1676Pichiecchio, A., Tavazzi, E., Poloni, G., Advanced magnetic resonance imaging of neuromyelitis optica: A multiparametric approach (2012) Mult Scler, 18, pp. 817-824Rocca, M.A., Agosta, F., Mezzapesa, D.M., Martinelli, V., Salvi, F., Ghezzi, A., Bergamaschi, R., Filippi, M., Magnetization transfer and diffusion tensor MRI show gray matter damage in neuromyelitis optica (2004) Neurology, 62 (3), pp. 476-478Merle, H., Olindo, S., Donnio, A., Retinal peripapillary nerve fiber layer thickness in neuromyelitis optica (2008) Invest Ophthalmol Vis Sci, 49, pp. 4412-4417De Seze, J., Blanc, F., Jeanjean, L., Zephir, H., Labauge, P., Bouyon, M., Ballonzoli, L., Speeg, C., Optical coherence tomography in neuromyelitis optica (2008) Archives of Neurology, 65 (7), pp. 920-923. , http://archneur.ama-assn.org/cgi/reprint/65/7/920, DOI 10.1001/archneur.65.7.920Green, A.J., Cree, B.A., Distinctive retinal nerve fibre layer and vascular changes in neuromyelitis optica following optic neuritis (2009) J Neurol Neurosurg Psychiatry, 80, pp. 1002-1005Ratchford, J.N., Quigg, M.E., Conger, A., Optical coherence tomography helps differentiate neuromyelitis optica and MS optic neuropathies (2009) Neurology, 73, pp. 302-308Wingerchuk, D.M., Lennon, V.A., Lucchinetti, C.F., Pittock, S.J., Weinshenker, B.G., The spectrum of neuromyelitis optica (2007) Lancet Neurology, 6 (9), pp. 805-815. , DOI 10.1016/S1474-4422(07)70216-8, PII S1474442207702168Von Glehn, F., Jarius, S., Penalva De Oliveira, A.C., Aquaporin-4 antibodies are not related to HTLV-1 associated myelopathy (2012) PLoS One, 7 (7), p. 39372Jarius, S., Probst, C., Borowski, K., Standardized method for the detection of antibodies to aquaporin-4 based on a highly sensitive immunofluorescence assay employing recombinant target antigen (2010) J Neurol Sci, 291, pp. 52-56Bendschneider, D., Tornow, R.P., Horn, F.K., Retinal nerve fiber layer thickness in normals measured by spectral domain OCT (2010) J Glaucoma, 19, pp. 475-482Smith, S.M., Jenkinson, M., Woolrich, M.W., Advances in functional and structural MR image analysis and implementation as FSL (2004) Neuroimage, 23, pp. 208-219Smith, S.M., Jenkinson, M., Johansen-Berg, H., Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data (2006) Neuroimage, 31, pp. 1487-1505Ashburner, J.A., A fast diffeomorphic image registration algorithm (2007) Neuroimage, 38, pp. 95-113Ashburner, J., Friston, K.J., Voxel-based morphometry - The methods (2000) NeuroImage, 11 (6), pp. 805-821. , DOI 10.1006/nimg.2000.0582Lancaster, J.L., Woldorff, M.G., Parsons, L.M., Liotti, M., Freitas, C.S., Rainey, L., Kochunov, P.V., Fox, P.T., Automated Talairach Atlas labels for functional brain mapping (2000) Human Brain Mapping, 10 (3), pp. 120-131. , DOI 10.1002/1097 -0193(200007) 10:3 3.0.CO;2-8Fischl, B., FreeSurfer (2012) Neuroimage, 62, pp. 774-781Genovese, C.R., Lazar, N.A., Nichols, T., Thresholding of statistical maps in functional neuroimaging using the false discovery rate (2002) NeuroImage, 15 (4), pp. 870-878. , DOI 10.1006/nimg.2001.1037Wingerchuk, D.M., Neuromyelitis optica: Effect of gender (2009) J Neurol Sci, 286, pp. 18-23Jarius, S., Paul, F., Franciotta, D., Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: Results from 211 lumbar punctures (2011) J Neurol Sci, 306, pp. 82-90Merle, H., Olindo, S., Bonnan, M., Natural history of the visual impairment of relapsing neuromyelitis optica (2007) Ophthalmology, 114, pp. 810-805Kitley, J., Leite, M.I., Nakashima, I., Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan (2012) Brain, 135, pp. 1834-1849Ciccarelli, O., Do cortical lesions help us to distinguish MS from NMO? (2012) Neurology, 79, pp. 1630-1631Yaguchi, H., Yabe, I., Takai, Y., Pathological study of subacute autoimmune encephalopathy with anti-AQP4 antibodies in a pregnant woman (2012) Mult Scler, 18, pp. 683-687Saji, E., Arakawa, M., Yanagawa, K., Cognitive impairment and cortical degeneration in neuromyelitis optica (2013) Ann Neurol, 73, pp. 65-76Gelfand, J.M., Nolan, R., Schwartz, D.M., Microcystic macular oedema in multiple sclerosis is associated with disease severity (2012) Brain, 135, pp. 1786-1793Kaufhold, F., Zimmermann, H., Schneider, E., Optic neuritis is associated with inner nuclear layer thickening and microcystic macular edema independently of multiple sclerosis (2013) PLoS One, 8 (8), p. 7114