Benefit of repetitive intrathecal triamcinolone acetonide therapy in predominantly spinal multiple sclerosis: prediction by upper spinal cord atrophy

Lukas, Carsten; Bellenberg, Barbara; Hahn, Horst K.; Rexilius, Jan; Drescher, Robert; Hellwig, Kerstin; Köster, O.; Schimrigk, Sebastian

doi:10.1177/1756285609343480

Cited by 16 publications

(9 citation statements)

References 22 publications

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“…Nonetheless, a marker—ideally derived from neurological laboratory routine diagnostic like CSF cell number or total protein—that stratifies responders and non-responders to ICT, may help to assign patients to this therapy. In accordance with previous studies we could stratify clinical data for a positive therapy response to ICT (16).…”

Section: Discussionsupporting

confidence: 80%

Predictors for Therapy Response to Intrathecal Corticosteroid Therapy in Multiple Sclerosis

et al. 2019

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Objective: The autoimmune disease Multiple Sclerosis (MS) represents a heterogeneous disease pattern with an individual course that may lead to permanent disability. In addition to immuno-modulating therapies patients benefit from symptomatic approaches like intrathecal corticosteroid therapy (ICT), which is frequently applied in a growing number of centers in Germany. ICT reduces spasticity, which elongates patient's walking distance and speed, thus improves quality of life. Methods: In our study we set out to investigate cerebrospinal fluid (CSF) parameters and clinical predictors for response to ICT. Therefore, we analyzed 811 CSF samples collected from 354 patients over a time period of 12 years. Patients who received ICT were divided in two groups (improving or active group) depending on their EDSS-progress. As control groups we analyzed data of ICT naïve patients, who were divided in the two groups as well. Additionally we observed the clinical progress after receiving ICT by comparison of patients in both groups. Results: The results showed clinical data had a significant influence on the probability to benefit from ICT. The probability (shown by Odds Ratio of 1.77–2.43) to belong to the improving group in contrast to the active group is significantly ( p < 0.0001) higher at later stages of disease with early disease onset (< 35 years, OR = 2.43) and higher EDSS at timepoint of ICT-initiation (EDSS > 6, OR = 2.06). Additionally, we observed lower CSF cell counts (6.68 ± 1.37 μl) and lower total CSF protein (412 ± 18.25 mg/l) of patients who responded to ICT compared to patients who did not ( p < 0.05). In the control group no significant differences were revealed. Furthermore analyses of our data revealed patients belonging to the improving group reach an EDSS of 6 after ICT-initiation less often than patients of the active group (after 13 years 39.8% in the improving group, 67.8% in the active group). Conclusion: Our study implies two relevant messages: (i) although the study was not designed to prospectively assess clinical data, in this cohort no severe side effects were observed under ICT; (ii) disease onset, EDSS, CSF cell count, and total protein may serve as predictive markers for therapy response.

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Section: Discussionsupporting

confidence: 80%

Predictors for Therapy Response to Intrathecal Corticosteroid Therapy in Multiple Sclerosis

et al. 2019

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“…and B.B., both with more than 8 years of experience) on each available sagittal threedimensional T1-weighted brain data set on which the upper cervical cord was visible with sufficient image quality. Images were postprocessed by using a semiautomated volumetry method (Neu-roQLab; Fraunhofer MEVIS, Bremen, Germany) (33,34). Briefly, volumes of interest with a fixed section length of 30 mm were placed on the sagittal three-dimensional T1-weighted images, starting at the upper border of vertebral level C2 (Figs 3, 4).…”

Section: Discussionmentioning

confidence: 99%

Relevance of Spinal Cord Abnormalities to Clinical Disability in Multiple Sclerosis: MR Imaging Findings in a Large Cohort of Patients

Lukas¹,

Sombekke²,

Bellenberg³

et al. 2013

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Purpose:To determine whether spinal cord atrophy differs among disease subtypes in multiple sclerosis (MS) and whether it offers diagnostic and clinical correlative information beyond that provided by other magnetic resonance (MR) imaging markers. Materials and Methods:The institutional review board approved the study; all subjects gave written informed consent. Upper cervical cord cross-sectional area (UCCA), brain and spinal cord lesion loads, and brain atrophy were measured in 440 patients with MS (311 with relapsing-remitting [RR] MS, 92 with secondary-progressive [SP] MS, and 37 with primary-progressive [PP] MS) studied in two centers. Disability was scored with the Expanded Disability Status Scale (EDSS), the timed 25-foot walk test (TWT), and the nine-hole peg test. UCCA was compared between groups with the Mann-Whitney U test. Correlations were assessed with the Spearman r test. Multivariate associations between UCCA and clinical and other MR imaging parameters, including number of hypointense brain lesions on T1-weighted MR images, presence of diffuse abnormalities, and number of involved segments in the spinal cord, were assessed by using multiple linear regression, adjusted for study center site. Results:The UCCA in patients with SP MS (median, 79 mm 2 ; interquartile range, 72.4-84.9 mm 2 ) and PP MS (median, 77.3 mm 2 ; interquartile range, 69-82.5 mm 2 ) was significantly smaller (P , .001) than that in patients with RR MS (median, 84 mm 2 ; interquartile range, 78.7-89.3 mm 2 ). UCCA was inversely correlated with EDSS score, TWT, and nine-hole peg test findings (r  20.29, P , .001 for all comparisons). UCCA, number of hypointense brain lesions on T1-weighted MR images, presence of diffuse abnormalities, and number of involved segments in the spinal cord were found to be significant explanatory factors for clinical disability (R 2 = 0.564). The UCCA and the number of hypointense brain lesions on T1-weighted images were the strongest MR imaging parameters for explaining physical disability, as measured with the EDSS. Conclusion:Spinal cord abnormalities have a strong effect on clinical disability in MS. MR imaging-derived UCCA was found to be the most significant spinal cord parameter for explaining EDSS score.q RSNA, 2013

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“…NeuroQLab (MeVisLab, Fraunhofer Mevis, Bremen, Germany) also provides a semi-automated method for cervical cord segmentation (Lukas et al, 2009). For this, the user selects a cuboid ROI manually, after which interactive watershed transformation (IWT) is applied to the image, removing non-CNS matter.…”

Section: Methodsmentioning

confidence: 99%

Validation of mean upper cervical cord area (MUCCA) measurement techniques in multiple sclerosis (MS): High reproducibility and robustness to lesions, but large software and scanner effects

Weeda

Middelkoop

Steenwijk

et al. 2019

NeuroImage: Clinical

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Introduction Atrophy of the spinal cord is known to occur in multiple sclerosis (MS). The mean upper cervical cord area (MUCCA) can be used to measure this atrophy. Currently, several (semi-)automated methods for MUCCA measurement exist, but validation in clinical magnetic resonance (MR) images is lacking. Methods Five methods to measure MUCCA (SCT-PropSeg, SCT-DeepSeg, NeuroQLab, Xinapse JIM and ITK-SNAP) were investigated in a predefined upper cervical cord region. First, within-scanner reproducibility and between-scanner robustness were assessed using intra-class correlation coefficient (ICC) and Dice's similarity index (SI) in scan-rescan 3DT1-weighted images (brain, including cervical spine using a head coil) performed on three 3 T MR machines (GE MR750, Philips Ingenuity, Toshiba Vantage Titan) in 21 subjects with MS and 6 healthy controls (dataset A). Second, sensitivity of MUCCA measurement to lesions in the upper cervical cord was assessed with cervical 3D T1-weighted images (3 T GE HDxT using a head-neck-spine coil) in 7 subjects with MS without and 14 subjects with MS with cervical lesions (dataset B), using ICC and SI with manual reference segmentations. Results In dataset A, MUCCA differed between MR machines ( p < 0.001) and methods ( p < 0.001) used, but not between scan sessions. With respect to MUCCA values, Xinapse JIM showed the highest within-scanner reproducibility (ICC absolute agreement = 0.995) while Xinapse JIM and SCT-PropSeg showed the highest between-scanner robustness (ICC consistency = 0.981 and 0.976, respectively). Reproducibility of segmentations between scan sessions was highest in Xinapse JIM and SCT-PropSeg segmentations (median SI ≥ 0.921), with a significant main effect of method ( p < 0.001), but not of MR machine or subject group. In dataset B, SI with manual outlines did not differ between patients with or without cervical lesions for any of the segmentation methods ( p > 0.176). However, there was an effect of method for both volumetric and voxel wise agreement of the segmentations (both p < 0.001). Highest volumetric and voxel wise agreement was obtained with Xinapse JIM (ICC absolute agreement = 0.940 and median SI = 0.962). Conclusion Although MUCCA is highly reproducible within a scanner for each individual measurement method, MUCCA differs between scanners and between methods. Cervical cord lesions do not affect MUCCA measurement performance.

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Benefit of repetitive intrathecal triamcinolone acetonide therapy in predominantly spinal multiple sclerosis: prediction by upper spinal cord atrophy

Cited by 16 publications

References 22 publications

Predictors for Therapy Response to Intrathecal Corticosteroid Therapy in Multiple Sclerosis

Predictors for Therapy Response to Intrathecal Corticosteroid Therapy in Multiple Sclerosis

Relevance of Spinal Cord Abnormalities to Clinical Disability in Multiple Sclerosis: MR Imaging Findings in a Large Cohort of Patients

Validation of mean upper cervical cord area (MUCCA) measurement techniques in multiple sclerosis (MS): High reproducibility and robustness to lesions, but large software and scanner effects

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