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.
- 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: An association between lipid measures and cognitive decline in patients with multiple sclerosis (MS) has been suggested. OBJECTIVES: This study aimed to investigate relationships between lipid profile and cognitive performance in a large observational cohort of MS patients. MATERIALS AND METHODS: We included 211 patients with 316 available pairs of lipid and cognitive measures performed over follow-up. The time between lipid and cognitive measures did not exceed 90 days. Baseline data were analyzed by non-parametric Spearman rank correlation test. Repeated measures were analyzed using linear mixed models adjusted for sex, age, education level, disease-modifying therapy status, and depression. RESULTS: Baseline analyses showed a correlation between higher low-density lipoprotein cholesterol (LDL-C) and lower Categorical Verbal Learning Test (CVLT) (rho=-0.15; p = 0.04), lower Symbol Digit Modalities Test (SDMT) (rho=-0.16; p = 0.02) and lower Brief Visuospatial Memory Test-Revised (BVMT-R) scores (rho=-0.12; p = 0.04). Higher high-density lipoprotein cholesterol (HDL-C) was negatively correlated with lower SDMT scores (rho=-0.16; p = 0.02) and lower Paced Auditory Serial Addition Test-3 (PASAT-3) scores (rho=-0.24; p = 0.03). Mixed model analyses of repeated measures showed a negative association between higher LDL-C and lower CVLT (B=-0.02; p < 0.001, Cohen ́s d = 0.08) and lower BVMT-R (B=-0.01; p = 0.03, Cohen ́s d=-0.12). Also, the negative association between HDL-C and PASAT-3 was confirmed in the mixed model analysis (B=-0.18; p = 0.01, Cohen ́s d = 0.07). Additional adjustments of the models for disability assessed by Expanded Disability Status Scale or Normalized Brain Volume did not change the results of the models substantially. CONCLUSIONS: Our results suggest a mild negative impact of dyslipidemia on cognitive performance in patients with MS. We propose that dyslipidemia contributes, at least in part, to cognitive decline in MS patients, independent of brain atrophy.
- MeSH
- dospělí MeSH
- HDL-cholesterol krev MeSH
- kognice fyziologie MeSH
- kognitivní dysfunkce * etiologie krev patofyziologie MeSH
- LDL-cholesterol * krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- neuropsychologické testy MeSH
- roztroušená skleróza * krev komplikace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
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.
- 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
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.
- 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
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.
- 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.
- 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
The translational potential of MR-based connectivity modelling is limited by the need for advanced diffusion imaging, which is not part of clinical protocols for many diseases. In addition, where diffusion data is available, brain connectivity analyses rely on tractography algorithms which imply two major limitations. First, tracking algorithms are known to be sensitive to the presence of white matter lesions and therefore leading to interpretation pitfalls and poor inter-subject comparability in clinical applications such as multiple sclerosis. Second, tractography quality is highly dependent on the acquisition parameters of diffusion sequences, leading to a trade-off between acquisition time and tractography precision. Here, we propose an atlas-based approach to study the interplay between structural disconnectivity and lesions without requiring individual diffusion imaging. In a multi-centric setting involving three distinct multiple sclerosis datasets (containing both 1.5 T and 3 T data), we compare our atlas-based structural disconnectome computation pipeline to disconnectomes extracted from individual tractography and explore its clinical utility for reducing the gap between radiological findings and clinical symptoms in multiple sclerosis. Results using topological graph properties showed that overall, our atlas-based disconnectomes were suitable approximations of individual disconnectomes from diffusion imaging. Small-worldness was found to decrease for larger total lesion volumes thereby suggesting a loss of efficiency in brain connectivity of MS patients. Finally, the global efficiency of the created brain graph, combined with total lesion volume, allowed to stratify patients into subgroups with different clinical scores in all three cohorts.
BACKGROUND: Basal ganglia lesions are typical findings on magnetic resonance imaging (MRI) of the brain in survivors of acute methanol poisoning. However, no data are available on the association between the magnitude of damaged brain regions, serum concentrations of markers of acute methanol toxicity, oxidative stress, neuroinflammation, and the rate of retinal nerve ganglion cell loss. OBJECTIVES: To investigate the association between MRI-based volumetry of the basal ganglia, retinal nerve fibre layer (RNFL) thickness and prognostic laboratory markers of outcomes in acute methanol poisoning. METHODS: MRI-based volumetry of putamen, nucleus caudatus and globus pallidus was performed and compared with laboratory parameters of severity of poisoning and acute serum markers of oxidative damage of lipids (8-isoprostan, MDA, HHE, HNE), nucleic acids (8-OHdG, 8-OHG, 5-OHMU), proteins (o-Thyr, NO-Thyr, Cl-Thyr) and leukotrienes (LTC4, LTD4, LTE4, LTB4), as well as with the results of RNFL measurements by optic coherence tomography (OCT) in 16 patients with acute methanol poisoning (Group I) and in 28 survivors of poisoning two years after discharge with the same markers measured within the follow-up examination (Group II). The control group consisted of 28 healthy subjects without methanol poisoning. RESULTS: The survivors of acute methanol poisoning had significantly lower volumes of basal ganglia than the controls. The patients with MRI signs of methanol-induced toxic brain damage had significantly lower volumes of basal ganglia than those without these signs. A positive correlation was found between the volume of putamen and arterial blood pH on admission (r = 0.45; p = 0.02 and r = 0.44; p = 0.02 for left and right putamen, correspondingly). A negative correlation was present between the volumes of putamen and acute serum lactate (r = -0.63; p < 0.001 and r = -0.59; p = 0.01), creatinine (r = -0.53; p = 0.01 and r = -0.47; p = 0.01) and glucose (r = -0.55; p < 0.001 and r = -0.50; p = 0.01) concentrations. The volume of basal ganglia positively correlated with acute concentrations of markers of lipoperoxidation (8-isoprostan: r = 0.61; p < 0.05 and r = 0.59; p < 0.05 for left and right putamen, correspondingly) and inflammation (leukotriene LTB4: r = 0.61; p < 0.05 and r = 0.61; p < 0.05 for left and right putamen, correspondingly). The higher the volume of the basal ganglia, the higher the thickness of the RNFL, with the strongest positive association between global RNFL and the volume of putamen bilaterally (all p < 0.01). In the follow-up markers of oxidative stress and inflammation, only o-Thyr concentration negatively correlated with the volume of putamen bilaterally (r = -0.39; p < 0.05 and r = -0.37; p < 0.05 for left and right putamen, correspondingly). CONCLUSION: In survivors of acute methanol poisoning with signs of toxic brain damage, the magnitude of affected areas correlated with acute parameters of severity of poisoning, markers of oxidative stress and neuroinflammation. There was a positive association between the basal ganglia volume and the thickness of RNFL, making OCT an important screening test and MRI-based volumetry the confirmative diagnostic method for the detection of CNS sequelae of methanol poisoning.
- MeSH
- bazální ganglia diagnostické zobrazování účinky léků metabolismus MeSH
- biologické markery krev MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- mediátory zánětu krev MeSH
- methanol otrava MeSH
- nervová vlákna účinky léků MeSH
- optická koherentní tomografie * MeSH
- otrava krev diagnostické zobrazování MeSH
- oxidační stres MeSH
- prediktivní hodnota testů MeSH
- retina diagnostické zobrazování účinky léků metabolismus MeSH
- studie případů a kontrol MeSH
- stupeň závažnosti nemoci MeSH
- velikost orgánu 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: Acute methanol poisoning leads to optic neuropathy and necrotic lesions of basal ganglia (BG) and subcortical white matter. Survivors of methanol poisoning exhibit long-term executive and memory deficits. Associations between brain volumetry parameters and cognitive sequelae of methanol poisoning are not known. The aim of our study was to identify long-term associations between the cognitive performance of survivors of methanol poisoning and the volume of the brain structures that are selectively vulnerable to methanol. METHODS: We conducted a cross-sectional follow-up study on a sample of patients (n = 33, age 50 ± 14 years, 82% males) who survived acute methanol poisoning during methanol mass poisoning outbreak from September 2012 till January 2013 in the Czech Republic. A battery of neuropsychological tests and brain magnetic resonance imaging were included in the clinical examination protocol. Specific brain structures (putamen, globus pallidus, nucleus caudatus, and frontal white matter) were selected as regions of interest, and their volumes were estimated using the MorphoBox prototype software. RESULTS: In robust multiple regression models, sustained visual attention performance (as assessed by Trail Making Test and Prague Stroop Test) was positively associated with BG structures and frontal white matter volumes (Wald = 9.03 to 85.50, p < 0.01), sensitivity to interference (as assessed by Frontal Battery Assessment) was negatively associated with frontal white matter volume (Wald = 35.44 to 42.25, p < 0.001), and motor performance (as assessed by Finger Tapping Test) was positively associated with globus pallidus and frontal white matter volumes (Wald = 9.66 to 13.29, p < 0.01). CONCLUSIONS: Our results demonstrate that smaller volumes of elements of BG-thalamocortical circuitry, namely the BG and frontal white matter, relate to attention and motor performance in methanol poisoning from a long-term perspective. Disruption of those functional circuits may underlie specific cognitive deficits observed in methanol poisoning.
- MeSH
- bazální ganglia diagnostické zobrazování MeSH
- bílá hmota diagnostické zobrazování MeSH
- dospělí MeSH
- exekutivní funkce účinky léků MeSH
- kognice účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- methanol otrava MeSH
- mozek diagnostické zobrazování MeSH
- následné studie MeSH
- nervová síť diagnostické zobrazování MeSH
- neuropsychologické testy MeSH
- paměť účinky léků MeSH
- pozornost účinky léků MeSH
- přežívající MeSH
- průřezové studie MeSH
- psychomotorický výkon účinky léků MeSH
- senioři MeSH
- učení účinky léků MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
