Metabolites in NAWM and lesion load in the visual pathways in MS patients.

<p><b>Metabolites</b>, N-Acetyl-Aspartate (NAA), Choline (Cho) and creatine (Cr) given in mM; <b>lesion load in the visual pathways</b>, here given as ratio of lesion volume in the visual pathways (AD, right anterior; AS, left anterior; PD, right posterior; PS, left posterior and total lesion volume) to total brain volume.</p><p>Metabolites in NAWM and lesion load in the visual pathways in MS patients.</p

RNFL in MS patients.

<p><b>Retinal sectors: OD</b>, right eye; <b>OS</b>, left eye; <b>G</b>, global; <b>S</b>, superior; <b>I</b>, inferior; <b>T</b>, temporal; <b>TS</b>, temporal superior; <b>TI</b>, temporal inferior; <b>N</b>, nasal; <b>NS</b>, nasal superior; <b>NI</b>, nasal inferior. All values are given in μm.</p><p>RNFL in MS patients.</p

Brain atrophy indices in MS patients.

<p><b>CHI</b>, the caudate head index; <b>BCI</b>, the basal cistern index; <b>CMI</b>, the cella media index; <b>MIF</b>, the maximum width of the anterior interhemispheric fissure; <b>MSF</b>, the maximum width of the Sylvian fissure; and <b>MFSS</b>, the maximum frontal subarachnoid space.</p><p>Brain atrophy indices in MS patients.</p

Regression Analysis.

<p><u>Simple regression–linear model: Independent variable</u>, RNFL; <u>dependent variables</u>, NAA, N-acetyl-aspartate; Cho, choline; Cr, creatine; LL per BV, lesionload per Brain Volume, LL AR, lesion load along anterior right visual pathway; LL AL, lesion load along anterior left visual pathway; LL PR, load along posterior right visual pathway; LL PL, load along posterior left visual pathway; Evan’s Index; CHI; CMI; BCI; the maximum width of the 3^rd ventricle; the maximum width of the 4^th ventricle; MIF, the maximum width of the anterior interhemispheric fissure; MFSS, the maximum frontal subarachnoid space; MSF, the maximum width of the Sylvian fissure; DD, disease duration; EDSS, expanded disability severity scale. <b>1</b>^<b>st</b><b>row</b>: all right eyes (n = 28; with and without ON) of all included MS patient. <b>2</b>^<b>nd</b><b>row</b>: all left eyes (n = 28; with and without ON) of all included MS patient. <b>3</b>^<b>rd</b><b>row</b>: all right eyes of MS patients who never experienced an ON (neither on their right nor on their left eye; RRMS, n = 17, SPMS, n = 2; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142272#pone.0142272.t001" target="_blank">Table 1</a>). <b>4</b>^<b>th</b><b>row</b>: all left eyes of MS patients who never experienced an ON (neither on their left nor on their right eye; RRMS, n = 17, SPMS, n = 2; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142272#pone.0142272.t001" target="_blank">Table 1</a>). Patients are the same as in the 3^rd row. <b>5</b>^<b>th</b><b>row</b>: right eyes of 6 MS patients who experienced an ON on their right eyes (note, 4 out of 6 experienced ON on both eyes, 2 only on their right eyes; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142272#pone.0142272.t001" target="_blank">Table 1</a>). <b>6</b>^<b>th</b><b>row</b>: left eyes of 6 MS patients who experienced an ON on their left eyes (note, 4 out of 7 experienced ON on both eyes, 3 only on their left eyes <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142272#pone.0142272.t001" target="_blank">Table 1</a>). For each analysis the correlation coefficient (corr. coeff.), R-squared (percent), the standard error of estimate (STE of Est.) and the p-value (analysis of variance, ANOVA) is given. Since the p-value in the ANOVA table is less than 0.01, there is a statistically significant relationship between the maximum width of the 4^th ventricle and the RNFL (for all patients’ right eyes, n = 28, 1^st row and for all patient’s left eyes, who never experienced ON, n = 17, 4^th row) at 99% confidence level. However, the low correlation coefficient indicates that there is only a weak relationship between the variables. R-squared statistic indicates that the simple/linear regression explains only 24.92% (1^st row) or 28.68% (4^th row) of the variability of the independent variable. In all other analyses presented here (and performed for the six OCT-Sectors, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142272#sec006" target="_blank">material and methods</a> or <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142272#pone.0142272.t005" target="_blank">Table 5</a>) no statistically significant correlation could be found (data not shown).</p

Clinical data.

<p><b>ON</b>, <b>optic neuritis;</b></p><p><b>*</b>, relapses treated with high dose steroid pulse therapy; no included patient had an ON within 12 months prior to the beginning of the study;</p><p><b>GLAT</b>, glatiramer-acetate 20mg subcutaneous once daily; <b>MITOX</b>, mitoxantrone; <b>IFN(a)</b>, interferon beta 1a intramuscularly once per week; <b>IFN(b)</b>, interferon beta 1a (44μg) subcutaneous trice per week; <b>IFN(c)</b>, interferon beta 1b (250μg) subcutaneous alternate day. Most importantly, the disease activity remained high in further follow-up with a median observation period of 22 ± 0.5 months [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142272#pone.0142272.ref033" target="_blank">33</a>]. However, no significant reduction of either the RNFL or the TMV could be found in follow-up [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142272#pone.0142272.ref033" target="_blank">33</a>; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142272#pone.0142272.ref036" target="_blank">36</a>].</p><p>¹, discontinued (48mg mitoxantrone per m² body surface); <b>none</b>, neither specific immunomodulatory or immunsuppressive therapy, drug holiday;</p><p>², drug withdrawal 12 months before OCT examination;</p><p>³, drug withdrawal 6 months before OCT examination;</p><p>⁴, drug withdrawal 20 months before OCT examination;</p><p>⁵, high titres of anti-interferon autoantibodies, drug withdrawal 14 months before OCT examination;</p><p>⁶, mitoxantrone cumulative dose 96mg per m² body surface, drug withdrawal 10 months before OCT examination;</p><p>⁷, mitoxantrone cumulative dose 92mg per m² body surface, drug withdrawal 10 months before OCT examination;</p><p>⁸, mitoxantrone cumulative dose 92mg per m² body surface, drug withdrawal 26 months before OCT examination;</p><p>⁹, mitoxantrone cumulative dose 108mg per m² body surface, drug withdrawal 27 months before 1^st OCT examination.</p><p>Clinical data.</p

Staining pattern of a patients´ serum with NMO-IgG/AQP4-antibodies in rat brain.

<p>Patients´serum shows extensive labeling of the granular layer of the cerebellum (A). Note the reticular staining pattern, forming basket-shaped processes around cell bodies of Purkinje cells (arrow), and the glia limitans perivascularis (arrow heads) (B). Immunoreactivity of hippocampus shows laminar specificity with strongest staining in the stratum lacunosum moleculare (SLM), molecular layer of the dentate gyrus (ML) and a thin layer of AQP4-positivity in the subgranular zone (arrow heads) (C, D; rectangle in C enlarged in D). SO, stratum oriens; SP, stratum pyramidale; SR, stratum radiatum; DGC, dentate granule cell layer; H, hilus. Magnification: A, D x100; B, x400; C, x40; .</p

Descriptive epidemiological data, summary.

<div><p>OCB typing according to established criteria (type 1 - 5, Andersson et al., 1994; [12]). </p> <p><b>1</b>, OCB - type 3; </p> <p><b>2</b>, OCB - type 2 and 3; </p> <p><b>3</b>, in 3 NMO patients OCB changed (from negative to positive (types 2 and 3)).</p></div