BACKGROUND AND PURPOSE: White matter (WM) tract disruption impacts volume loss in connected deep gray matter (DGM) over 5 years in people with multiple sclerosis (PwMS). However, the timeline of this phenomenon remains poorly characterized. MATERIALS AND METHODS: Annual serial MRI for 181 PwMS was retrospectively analyzed from a 10-year clinical trial database. Annualized thalamic atrophy, DGM atrophy, and disruption of connected WM tracts were measured. For time series analysis, ~700 epochs were collated using a sliding 5-year window, and regression models predicting 1-year atrophy were applied to characterize the influence of new tract disruption from preceding years, while controlling for whole brain atrophy and other relevant factors. RESULTS: Disruptions of WM tracts connected to the thalamus were significantly associated with thalamic atrophy 1 year later (β: 0.048-0.103). This effect was not observed for thalamic tract disruption concurrent with the time of atrophy nor for thalamic tract disruption preceding the atrophy by 2-4 years. Similarly, disruptions of white matter tracts connected to the DGM were significantly associated with DGM atrophy 1 year later (β: 0.078-0.111), but not for tract disruption concurrent with, nor preceding the atrophy by 2-4 years. CONCLUSION: Increased rates of thalamic and DGM atrophy were restricted to 1 year following newly developed disruption in connected WM tracts. In research and clinical settings, additional gray matter atrophy may be expected 1 year following new lesion growth in connected white matter.

• Klíčová slova
• Atrophy, Degeneration, Lesions, Multiple sclerosis,
• MeSH
• atrofie patologie   MeSH
• bílá hmota * diagnostické zobrazování   patologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• retrospektivní studie MeSH
• roztroušená skleróza * komplikace   diagnostické zobrazování   patologie   MeSH
• šedá hmota diagnostické zobrazování   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: To describe the dynamics of brain volume loss (BVL) at different stages of relapsing-remitting multiple sclerosis (RRMS), to describe the association between BVL and clinical measures, and to investigate an effect of treatment escalation on the rate of BVL. METHODS: Together, 1903 patients predominantly with RRMS from the Avonex-Steroids-Azathioprine cohort (N = 166), the study of early IFN-β1a treatment cohort (N = 180), and the quantitative MRI cohort (N = 1,557) with ≥2 MRI scans and ≥1-year of follow-up were included. Brain MRI scans (N = 7,203) were performed using a single 1.5-T machine. Relationships between age or disease duration and global and tissue-specific BVL rates were analyzed using mixed models. RESULTS: Age was not associated with the rate of BVL (β = -0.003; Cohen f2 = 0.0005; adjusted p = 0.39). Although disease duration was associated with the rate of BVL, its effect on the BVL rate was minimal (β = -0.012; Cohen f2 = 0.004; adjusted p = 4 × 10-5). Analysis of association between tissue-specific brain volume changes and age (β = -0.019 to -0.011; adjusted p = 0.028-1.00) or disease duration (β = -0.028 to -0.008; adjusted p = 0.16-0.96) confirmed these results. Although increase in the relapse rate (β = 0.10; adjusted p = 9 × 10-9), Expanded Disability Status Scale (EDSS; β = 0.17; adjusted p = 8 × 10-5), and EDSS change (β = 0.15; adjusted p = 2 × 10-5) were associated with accelerated rate of BVL, their effect on the rate of BVL was minimal (all Cohen f2 ≤ 0.007). In 94 patients who escalated therapy, the rate of BVL decreased following treatment escalation by 0.29% (β = -0.29; Cohen f2 = 0.133; p = 5.5 × 10-8). CONCLUSIONS: The rate of BVL is relatively stable throughout the course of RRMS. The accelerated BVL is weakly associated with concurrent higher disease activity, and timely escalation to high-efficacy immunotherapy helps decrease the rate of BVL.

• MeSH
• atrofie patologie   MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie MeSH
• mozek patologie   MeSH
• progrese nemoci MeSH
• prospektivní studie MeSH
• roztroušená skleróza patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

At two meetings of a Central European board of multiple sclerosis (MS) experts in 2018 and 2019 factors influencing daily treatment choices in MS, especially practice guidelines, biomarkers and burden of disease, were discussed. The heterogeneity of MS and the complexity of the available treatment options call for informed treatment choices. However, evidence from clinical trials is generally lacking, particularly regarding sequencing, switches and escalation of drugs. Also, there is a need to identify patients who require highly efficacious treatment from the onset of their disease to prevent deterioration. The recently published European Committee for the Treatment and Research in Multiple Sclerosis/European Academy of Neurology clinical practice guidelines on pharmacological management of MS cover aspects such as treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and are based on expert consensus statements. However, the recommendations constitute an excellent framework that should be adapted to local regulations, MS center capacities and infrastructure. Further, available and emerging biomarkers for treatment guidance were discussed. Magnetic resonance imaging parameters are deemed most reliable at present, even though complex assessment including clinical evaluation and laboratory parameters besides imaging is necessary in clinical routine. Neurofilament-light chain levels appear to represent the current most promising non-imaging biomarker. Other immunological data, including issues of immunosenescence, will play an increasingly important role for future treatment algorithms. Cognitive impairment has been recognized as a major contribution to MS disease burden. Regular evaluation of cognitive function is recommended in MS patients, although no specific disease-modifying treatment has been defined to date. Finally, systematic documentation of real-life data is recognized as a great opportunity to tackle unresolved daily routine challenges, such as use of sequential therapies, but requires joint efforts across clinics, governments and pharmaceutical companies.

• Klíčová slova
• biomarkers, burden of disease, cognitive dysfunction, magnetic resonance imaging, multiple sclerosis, neurofilament,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND AND PURPOSE: Disappearance of T2 lesions into CSF spaces is frequently observed in patients with MS. Our aim was to investigate temporal changes of cumulative atrophied brain T2 lesion volume and 10-year confirmed disability progression. MATERIALS AND METHODS: We studied 176 patients with relapsing-remitting MS who underwent MR imaging at baseline, 6 months, and then yearly for 10 years. Occurrence of new/enlarging T2 lesions, changes in T2 lesion volume, and whole-brain, cortical and ventricle volumes were assessed yearly between baseline and 10 years. Atrophied T2 lesion volume was calculated by combining baseline lesion masks with follow-up CSF partial volume maps. Ten-year confirmed disability progression was confirmed after 48 weeks. ANCOVA detected MR imaging outcome differences in stable (n = 76) and confirmed disability progression (n = 100) groups at different time points; hierarchic regression determined the unique additive variance explained by atrophied T2 lesion volume regarding the association with confirmed disability progression, in addition to other MR imaging metrics. Cox regression investigated the association of early MR imaging outcome changes and time to development of confirmed disability progression. RESULTS: The separation of stable-versus-confirmed disability progression groups became significant even in the first 6 months for atrophied T2 lesion volume (140% difference, Cohen d = 0.54, P = .004) and remained significant across all time points (P ≤ .007). The hierarchic model, including all other MR imaging outcomes during 10 years predicting confirmed disability progression, improved significantly after adding atrophied T2 lesion volume (R 2 = 0.27, R 2 change 0.11, P = .009). In Cox regression, atrophied T2 lesion volume in 0-6 months (hazard ratio = 4.23, P = .04) and 0-12 months (hazard ratio = 2.41, P = .022) was the only significant MR imaging predictor of time to confirmed disability progression. CONCLUSIONS: Atrophied T2 lesion volume is a robust and early marker of disability progression in relapsing-remitting MS.

• MeSH
• atrofie diagnostické zobrazování   patologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• následné studie MeSH
• progrese nemoci MeSH
• recidiva MeSH
• relabující-remitující roztroušená skleróza diagnostické zobrazování   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: To investigate spatial patterns of gray matter (GM) atrophy and their association with disability progression in patients with early relapsing-remitting multiple sclerosis (MS) in a longitudinal setting. METHODS: Brain MRI and clinical neurological assessments were obtained in 152 MS patients at baseline and after 10 years of follow-up. Patients were classified into those with confirmed disability progression (CDP) (n = 85) and those without CDP (n = 67) at the end of the study. An optimized, longitudinal source-based morphometry (SBM) pipeline, which utilizes independent component analysis, was used to identify eight spatial patterns of common GM volume co-variation in a data-driven manner. GM volume at baseline and rates of change were compared between patients with CDP and those without CDP. RESULTS: The identified patterns generally included structurally or functionally related GM regions. No significant differences were detected at baseline GM volume between the sub-groups. Over the follow-up, patients with CDP experienced a significantly greater rate of GM atrophy within two of the eight patterns, after correction for multiple comparisons (corrected p-values of 0.001 and 0.007). The patterns of GM atrophy associated with the development of CDP included areas involved in motor functioning and cognitive domains such as learning and memory. CONCLUSION: SBM analysis offers a novel way to study the temporal evolution of regional GM atrophy. Over 10 years of follow-up, disability progression in MS is related to GM atrophy in areas associated with motor and cognitive functioning.

• Klíčová slova
• Atrophy, Disability, Gray matter, MRI, Multiple sclerosis,
• MeSH
• atrofie MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie MeSH
• mapování mozku MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• progrese nemoci * MeSH
• relabující-remitující roztroušená skleróza diagnostické zobrazování   patologie   MeSH
• šedá hmota diagnostické zobrazování   patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: A percent brain volume change (PBVC) cut-off of -0.4% per year has been proposed to distinguish between pathological and physiological changes in multiple sclerosis (MS). Unfortunately, standardized PBVC measurement is not always feasible on scans acquired outside research studies or academic centers. Percent lateral ventricular volume change (PLVVC) is a strong surrogate measure of PBVC, and may be more feasible for atrophy assessment on real-world scans. However, the PLVVC rate corresponding to the established PBVC cut-off of -0.4% is unknown. OBJECTIVE: To establish a pathological PLVVC expansion rate cut-off analogous to -0.4% PBVC. METHODS: We used three complementary approaches. First, the original follow-up-length-weighted receiver operating characteristic (ROC) analysis method establishing whole brain atrophy rates was adapted to a longitudinal ventricular atrophy dataset of 177 relapsing-remitting MS (RRMS) patients and 48 healthy controls. Second, in the same dataset, SIENA PBVCs were used with non-linear regression to directly predict the PLVVC value corresponding to -0.4% PBVC. Third, in an unstandardized, real world dataset of 590 RRMS patients from 33 centers, the cut-off maximizing correspondence to PBVC was found. Finally, correspondences to clinical outcomes were evaluated in both datasets. RESULTS: ROC analysis suggested a cut-off of 3.09% (AUC = 0.83, p < 0.001). Non-linear regression R2 was 0.71 (p < 0.001) and a - 0.4% PBVC corresponded to a PLVVC of 3.51%. A peak in accuracy in the real-world dataset was found at a 3.51% PLVVC cut-off. Accuracy of a 3.5% cut-off in predicting clinical progression was 0.62 (compared to 0.68 for PBVC). CONCLUSIONS: Ventricular expansion of between 3.09% and 3.51% on T2-FLAIR corresponds to the pathological whole brain atrophy rate of 0.4% for RRMS. A conservative cut-off of 3.5% performs comparably to PBVC for clinical outcomes.

• Klíčová slova
• Brain atrophy, Multiple sclerosis, NEDA, Pathological cutoff, Ventricular volume,
• MeSH
• databáze faktografické statistika a číselné údaje   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• nelineární dynamika MeSH
• počítačové zpracování obrazu MeSH
• posuzování pracovní neschopnosti MeSH
• progrese nemoci MeSH
• referenční hodnoty MeSH
• relabující-remitující roztroušená skleróza diagnostické zobrazování   patologie   MeSH
• ROC křivka MeSH
• stupeň závažnosti nemoci MeSH
• ventriculi laterales diagnostické zobrazování   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: There is a need for a brain volume measure applicable to the clinical routine scans. Nearly every multiple sclerosis (MS) protocol includes low-resolution 2D T2-FLAIR imaging. OBJECTIVES: To develop and validate cross-sectional and longitudinal brain atrophy measures on clinical-quality T2-FLAIR images in MS patients. METHODS: A real-world dataset from 109 MS patients from 62 MRI scanners was used to develop a lateral ventricular volume (LVV) algorithm with a longitudinal Jacobian-based extension, called NeuroSTREAM. Gold-standard LVV was calculated on high-resolution T1 1 mm, while NeuroSTREAM LVV was obtained on low-resolution T2-FLAIR 3 mm thick images. Scan-rescan reliability was assessed in 5 subjects. The variability of LVV measurement at different field strengths was tested in 76 healthy controls and 125 MS patients who obtained both 1.5T and 3T scans in 72 hours. Clinical validation of algorithm was performed in 176 MS patients who obtained serial yearly MRI 1.5T scans for 10 years. RESULTS: Correlation between gold-standard high-resolution T1 LVV and low-resolution T2-FLAIR LVV was r = 0.99, p < 0.001 and the scan-rescan coefficient of variation was 0.84%. Correlation between low-resolution T2-FLAIR LVV on 1.5T and 3T was r = 0.99, p < 0.001 and the scan-rescan coefficient of variation was 2.69% cross-sectionally and 2.08% via Jacobian integration. NeuroSTREAM showed comparable effect size (d = 0.39-0.71) in separating MS patients with and without confirmed disability progression, compared to SIENA and VIENA. CONCLUSIONS: Brain atrophy measurement on clinical quality T2-FLAIR scans is feasible, accurate, reliable, and relates to clinical outcomes.

• Klíčová slova
• Automated measurement, Brain atrophy, Multiple sclerosis, Ventricular volume,
• MeSH
• atrofie MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• průřezové studie MeSH
• radioisotopová scintigrafie MeSH
• reprodukovatelnost výsledků MeSH
• roztroušená skleróza diagnostické zobrazování   patologie   MeSH
• software MeSH
• ventriculi laterales patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH