BACKGROUND AND OBJECTIVES: In multiple sclerosis (MS), slowly expanding lesions were shown to be associated with worse disability and prognosis. Their timely detection from cross-sectional data at early disease stages could be clinically relevant to inform treatment planning. Here, we propose to use multiparametric, quantitative MRI to allow a better cross-sectional characterization of lesions with different longitudinal phenotypes. METHODS: We analysed T1 and T2 relaxometry maps from a longitudinal cohort of MS patients. Lesions were classified as enlarging, shrinking, new or stable based on their longitudinal volumetric change using a newly developed automated technique. Voxelwise deviations were computed as z-scores by comparing individual patient data to T1, T2 and T2/T1 normative values from healthy subjects. We studied the distribution of microstructural properties inside lesions and within perilesional tissue. RESULTS AND CONCLUSIONS: Stable lesions exhibited the highest T1 and T2 z-scores in lesion tissue, while the lowest values were observed for new lesions. Shrinking lesions presented the highest T1 z-scores in the first perilesional ring while enlarging lesions showed the highest T2 z-scores in the same region. Finally, a classification model was trained to predict the longitudinal lesion type based on microstructural metrics and feature importance was assessed. Z-scores estimated in lesion and perilesional tissue from T1, T2 and T2/T1 quantitative maps carry discriminative and complementary information to classify longitudinal lesion phenotypes, hence suggesting that multiparametric MRI approaches are essential for a better understanding of the pathophysiological mechanisms underlying disease activity in MS lesions.

• Klíčová slova
• Enlarging lesions, Lesion subtyping, Multiple sclerosis, Quantitative MRI, Relaxometry,
• MeSH
• dospělí MeSH
• fenotyp * MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• multiparametrická magnetická rezonance MeSH
• progrese nemoci MeSH
• průřezové studie MeSH
• 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

OBJECTIVE: The potential of magnetization transfer imaging (MTI) and diffusion tensor imaging (DTI) for the detection and evolution of new multiple sclerosis (MS) lesions was analyzed. METHODS: Nineteen patients with MS obtained conventional MRI, MTI, and DTI examinations bimonthly for 12 months and again after 24 months at 1.5 T MRI. MTI was acquired with balanced steady-state free precession (bSSFP) in 10 min (1.3 mm3 isotropic resolution) yielding both magnetization transfer ratio (MTR) and quantitative magnetization transfer (qMT) parameters (pool size ratio (F), exchange rate (kf), and relaxation times (T1/T2)). DTI provided fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). RESULTS: At the time of their appearance on MRI, the 21 newly detected MS lesions showed significantly reduced MTR/F/kf and prolonged T1/T2 parameters, as well as significantly reduced FA and increased AD/MD/RD. Significant differences were already observed for MTR 4 months and for qMT parameters 2 months prior to lesions' detection on MRI. DTI did not show any significant pre-lesional differences. Slightly reversed trends were observed for most lesions up to 8 months after their detection for qMT and less pronounced for MTR and three diffusion parameters, while appearing unchanged on MRI. CONCLUSIONS: MTI provides more information than DTI in MS lesions and detects tissue changes 2 to 4 months prior to their appearance on MRI. After lesions' detection, qMT parameter changes promise to be more sensitive than MTR for the lesions' evolutional assessment. Overall, bSSFP-based MTI adumbrates to be more sensitive than MRI and DTI for the early detection and follow-up assessment of MS lesions. CLINICAL RELEVANCE STATEMENT: When additionally acquired in routine MRI, fast bSSFP-based MTI can complement the MRI/DTI longitudinal lesion assessment by detecting MS lesions 2-4 months earlier than with MRI, which could implicate earlier clinical decisions and better follow-up/treatment assessment in MS patients. KEY POINTS: • Magnetization transfer imaging provides more information than DTI in multiple sclerosis lesions and can detect tissue changes 2 to 4 months prior to their appearance on MRI. • After lesions' detection, quantitative magnetization transfer changes are more pronounced than magnetization transfer ratio changes and therefore promise to be more sensitive for the lesions' evolutional assessment. • Balanced steady-state free precession-based magnetization transfer imaging is more sensitive than MRI and DTI for the early detection and follow-up assessment of multiple sclerosis lesions.

• Klíčová slova
• Balanced steady-state free precession, Diffusion tensor imaging, Magnetization transfer ratio, Multiple sclerosis, Quantitative magnetization transfer,
• MeSH
• anizotropie MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• roztroušená skleróza * diagnostické zobrazování   patologie   MeSH
• zobrazování difuzních tenzorů * metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Microstructural characterization of patients with multiple sclerosis (MS) has been shown to correlate better with disability compared to conventional radiological biomarkers. Quantitative MRI provides effective means to characterize microstructural brain tissue changes both in lesions and normal-appearing brain tissue. However, the impact of the location of microstructural alterations in terms of neuronal pathways has not been thoroughly explored so far. Here, we study the extent and the location of tissue changes probed using quantitative MRI along white matter (WM) tracts extracted from a connectivity atlas. METHODS: We quantified voxel-wise T1 tissue alterations compared to normative values in a cohort of 99 MS patients. For each WM tract, we extracted metrics reflecting tissue alterations both in lesions and normal-appearing WM and correlated these with cross-sectional disability and disability evolution after 2 years. RESULTS: In early MS patients, T1 alterations in normal-appearing WM correlated better with disability evolution compared to cross-sectional disability. Further, the presence of lesions in supratentorial tracts was more strongly associated with cross-sectional disability, while microstructural alterations in infratentorial pathways yielded higher correlations with disability evolution. In progressive patients, all major WM pathways contributed similarly to explaining disability, and correlations with disability evolution were generally poor. CONCLUSIONS: We showed that microstructural changes evaluated in specific WM pathways contribute to explaining future disability in early MS, hence highlighting the potential of tract-wise analyses in monitoring disease progression. Further, the proposed technique allows to estimate WM tract-specific microstructural characteristics in clinically compatible acquisition times, without the need for advanced diffusion imaging.

• Klíčová slova
• Demyelinating diseases, Magnetic resonance imaging, Multiple sclerosis, Relaxometry, White matter,
• MeSH
• bílá hmota * diagnostické zobrazování   patologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• průřezové studie MeSH
• roztroušená skleróza * diagnostické zobrazování   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Early diagnosis and treatment of patients with multiple sclerosis (MS) are associated with better outcomes; however, diagnostic delays remain a major problem. OBJECTIVE: Describe the prevalence, determinants and consequences of delayed diagnoses. METHODS: This single-centre ambispective study analysed 146 adult relapsing-remitting MS patients (2016-2021) for frequency and determinants of diagnostic delays and their associations with clinical, cognitive, imaging and biochemical measures. RESULTS: Diagnostic delays were identified in 77 patients (52.7%), including 42 (28.7%) physician-dependent cases and 35 (24.0%) patient-dependent cases. Diagnosis was delayed in 22 (15.1%) patients because of misdiagnosis by a neurologist. A longer diagnostic delay was associated with trends towards greater Expanded Disability Status Scale (EDSS) scores (B = 0.03; p = 0.034) and greater z-score of the blood neurofilament light chain (B = 0.35; p = 0.031) at the time of diagnosis. Compared with patients diagnosed at their first clinical relapse, patients with a history of >1 relapse at diagnosis (n = 63; 43.2%) had a trend towards greater EDSS scores (B = 0.06; p = 0.006) and number of total (B = 0.13; p = 0.040) and periventricular (B = 0.06; p = 0.039) brain lesions. CONCLUSION: Diagnostic delays in MS are common, often determined by early misdiagnosis and associated with greater disease burden.

• Klíčová slova
• Delayed diagnosis, brain lesion, cerebrospinal fluid, disability, magnetic resonance imaging, misdiagnosis, multiple sclerosis, neurofilament,
• MeSH
• dospělí MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek patologie   MeSH
• opožděná diagnóza MeSH
• prevalence MeSH
• recidiva MeSH
• relabující-remitující roztroušená skleróza * diagnóza   epidemiologie   patologie   MeSH
• roztroušená skleróza * diagnóza   epidemiologie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, mainly affecting young adults. Factors positively influencing its course include early antiinflammatory treatment and the influencing of other comorbidities. The most common comorbidities occurring in MS patients with a higher frequency than in the general population are neurological, psychiatric, cardiovascular, metabolic and autoimmune. Just as comorbidity compensation affects the course of MS, in some cases, MS decompensation is associated with a worse course of associated diseases. Due to common risk factors and partially shared immunopathogenesis, treatment covering multiple conditions can be used, especially for some autoimmune diseases. On the other hand, some drugs may potentiate the development of other autoimmunity or disorder. A special topic is the side effects and complications of treatment (especially infections and malignancies) of disease-modifying therapies used in patients with MS. However, the potential treatment discontinuation carries significant risks and should always be discussed with the MS specialist. Therefore, close interdisciplinary collaboration is crucial.

• Klíčová slova
• Drug interactions, adverse effects, autoimmune diseases, comorbidities, disease -modifying therapies, drug-drug interactions, multiple sclerosis, multiple sclerosis, side effects,
• MeSH
• chronická nemoc MeSH
• komorbidita MeSH
• lidé MeSH
• mladý dospělý MeSH
• rizikové faktory MeSH
• roztroušená skleróza * komplikace   farmakoterapie   epidemiologie   MeSH
• Check Tag
• lidé MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH

Dysphagia is a common symptom of neurological disease, including multiple sclerosis (MS). The DYsphagia in MUltiple Sclerosis (DYMUS) questionnaire was developed as a screening tool for swallowing problems. The purpose of the present study was to validate the Czech version of the DYMUS questionnaire. We validated the questionnaire on a sample of 435 patients with MS and 135 healthy controls (HC) chosen by accidental sampling from larger, long-term studies conducted by the Prague MS Center. For the purposes of this study, we used both electronic (primary method of distribution) and paper-based (backup) versions of the questionnaire. The internal consistency of the whole scale was satisfactory (Cronbach's α =0.833). The DYMUS mean score in HC was 0.215 (standard deviation [SD] = 0.776). Normative data suggested a cut-off value for dysphagia between 1 and 2 points. Principal component analysis (PCA) showed a two-factor structure of the adapted scale. However, the structure did not completely correspond to the originally proposed dimensions of dysphagia for solids and liquids; our data supported dropout of item Q10. Criterion validity was proved by the difference in dysphagia between HC and patients MS (U = 25,546, p < 0.001) and by a positive correlation with the EDSS (Kendall's tau-b = 0.169, p < 0.001) and other patient-reported outcomes. The Czech version of the DYMUS questionnaire is a valid and reliable tool for evaluating swallowing impairment in Czech-speaking patients with MS. Moreover, the questionnaire can be administered electronically, with a paper-based backup.

• Klíčová slova
• DYMUS, Dysphagia, Multiple sclerosis, Reliability, Validity,
• MeSH
• hodnocení výsledků péče pacientem MeSH
• lidé MeSH
• poruchy polykání * diagnóza   etiologie   MeSH
• průzkumy a dotazníky MeSH
• reprodukovatelnost výsledků MeSH
• roztroušená skleróza * komplikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

• Publikační typ
• tisková chyba MeSH

BACKGROUND: COVID-19 vaccination and infection are speculated to increase the activity of immune-mediated diseases, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The aim of this study was to evaluate a short-term risk of relapse after COVID-19 vaccination and COVID-19 infection in patients with these demyelinating disorders of the central nervous system and to determine disease exacerbation risk factors. METHODS: Data in this retrospective, observational cohort study was collected via the Czech nationwide registry ReMuS from March 1, 2020, to October 30, 2021. We compared the proportion of patients with at least one clinical relapse in the 90 days following vaccination or infection to the 90-day intervals during the year before. For the evaluation of the risk factors of relapse, a comparison between groups with and without relapses after COVID-19 vaccination or infection was made. RESULTS: We identified 1661 vaccinated (90.11% BNT162b2) patients with MS without a history of COVID-19 and 495 unvaccinated patients with MS who experienced COVID-19. A mild increase in the proportion of patients with at least one clinical relapse (-360 to -270 days: 4.46%; -270 to -180: 4.27%; -180 to -90: 3.85%; -90 to 0: 3.79% vs. 0 to +90 days: 5.30%) after vaccination in patients with MS was observed, as well as a rise in the proportion of patients with at least one clinical relapse after COVID-19. Lower age was associated with MS relapse after vaccination or infection. Although there were only 17 vaccinated and eight post-COVID-19 patients with NMOSD, the results were broadly consistent with those of patients with MS. CONCLUSION: There is a mild increase in the relapse incidence after the COVID-19 vaccination. The risks, however, need to be balanced against the risks of COVID-19 itself, also leading to the rise in relapse rate and particularly to morbidity and mortality.

• Klíčová slova
• Acute relapse, COVID-19, Multiple sclerosis, Neuromyelitis optica, Vaccination,
• MeSH
• COVID-19 * prevence a kontrola   MeSH
• lidé MeSH
• neuromyelitis optica * komplikace   MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• roztroušená skleróza * komplikace   MeSH
• vakcína BNT162 MeSH
• vakcinace škodlivé účinky   MeSH
• vakcíny proti COVID-19 * škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• vakcína BNT162 MeSH
• vakcíny proti COVID-19 * MeSH

BACKGROUND: Early infratentorial and focal spinal cord lesions on magnetic resonance imaging (MRI) are associated with a higher risk of long-term disability in patients with multiple sclerosis (MS). The role of diffuse spinal cord lesions remains less understood. The purpose of this study was to evaluate focal and especially diffuse spinal cord lesions in patients with early relapsing-remitting MS and their association with intracranial lesion topography, global and regional brain volume, and spinal cord volume. METHODS: We investigated 58 MS patients with short disease duration (< 5 years) from a large academic MS center and 58 healthy controls matched for age and sex. Brain, spinal cord, and intracranial lesion volumes were compared among patients with- and without diffuse spinal cord lesions and controls. Binary logistic regression models were used to analyse the association between the volume and topology of intracranial lesions and the presence of focal and diffuse spinal cord lesions. RESULTS: We found spinal cord involvement in 75% of the patients (43/58), including diffuse changes in 41.4% (24/58). Patients with diffuse spinal cord changes exhibited higher volumes of brainstem lesion volume (p = 0.008). The presence of at least one brainstem lesion was associated with a higher probability of the presence of diffuse spinal cord lesions (odds ratio 47.1; 95% confidence interval 6.9-321.6 p < 0.001) as opposed to focal spinal cord lesions (odds ratio 0.22; p = 0.320). Patients with diffuse spinal cord lesions had a lower thalamus volume compared to patients without diffuse spinal cord lesions (p = 0.007) or healthy controls (p = 0.002). CONCLUSIONS: Diffuse spinal cord lesions are associated with the presence of brainstem lesions and with a lower volume of the thalamus. This association was not found in patients with focal spinal cord lesions. If confirmed, thalamic atrophy in patients with diffuse lesions could increase our knowledge on the worse prognosis in patients with infratentorial and SC lesions.

• Klíčová slova
• Focal and diffuse lesions, thalamus, Infratentorial lesions, Multiple sclerosis, Spinal cord,
• MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mícha diagnostické zobrazování   patologie   MeSH
• mozek patologie   MeSH
• mozkový kmen diagnostické zobrazování   patologie   MeSH
• nemoci míchy * patologie   MeSH
• posuzování pracovní neschopnosti MeSH
• relabující-remitující roztroušená skleróza * diagnostické zobrazování   patologie   MeSH
• roztroušená skleróza * diagnostické zobrazování   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Pathology in multiple sclerosis is not homogenously distributed. Recently, it has been shown that structures adjacent to CSF are more severely affected. A gradient of brain tissue involvement was shown with more severe pathology in periventricular areas and in proximity to brain surfaces such as the subarachnoid spaces and ependyma, and hence termed the "surface-in" gradient. Here, we study whether (i) the surface-in gradient of periventricular tissue alteration measured by T1 relaxometry is already present in early multiple sclerosis patients, (ii) how it differs between early and progressive multiple sclerosis patients, and (iii) whether the gradient-derived metrics in normal-appearing white matter and lesions correlate better with physical disability than conventional MRI-based metrics. METHODS: Forty-seven patients with early multiple sclerosis, 52 with progressive multiple sclerosis, and 92 healthy controls were included in the study. Isotropic 3D T1 relaxometry maps were obtained using the Magnetization-Prepared 2 Rapid Acquisition Gradient Echoes sequence at 3 T. After spatially normalizing the T1 maps into a study-specific common space, T1 inter-subject variability within the healthy cohort was modelled voxel-wise, yielding a normative T1 atlas. Individual comparisons of each multiple sclerosis patient against the atlas were performed by computing z-scores. Equidistant bands of voxels were defined around the ventricles in the supratentorial white matter; the z-scores in these bands were analysed and compared between the early and progressive multiple sclerosis cohorts. Correlations between both conventional and z-score-gradient-derived MRI metrics and the Expanded Disability Status Scale were assessed. RESULTS: Patients with early and progressive multiple sclerosis demonstrated a periventricular gradient of T1 relaxation time z-scores. In progressive multiple sclerosis, z-score-derived metrics reflecting the gradient of tissue abnormality in normal-appearing white matter were more strongly correlated with disability (maximal rho = 0.374) than the conventional lesion volume and count (maximal rho = 0.189 and 0.21 respectively). In early multiple sclerosis, the gradient of normal-appearing white matter volume with z-scores > 2 at baseline correlated with clinical disability assessed at two years follow-up. CONCLUSION: Our results suggest that the surface-in white matter gradient of tissue alteration is detectable with T1 relaxometry and is already present at clinical disease onset. The periventricular gradients correlate with clinical disability. The periventricular gradient in normal-appearing white matter may thus qualify as a promising biomarker for monitoring of disease activity from an early stage in all phenotypes of multiple sclerosis.

• Klíčová slova
• Atlas-based assessment, Gradient of tissue damage, MP2RAGE, Multiple sclerosis, T(1)-relaxometry,
• MeSH
• bílá hmota * diagnostické zobrazování   patologie   MeSH
• chronicko-progresivní roztroušená skleróza patologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• roztroušená skleróza * diagnostické zobrazování   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH