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Objectives: The purpose of this work was to evaluate the influence of residual quadrupolar interaction on the determination of human brain apparent tissue sodium concentrations (aTSCs) using quantitative sodium magnetic resonance imaging ( 23 Na MRI) in healthy controls (HCs) and patients with multiple sclerosis (MS). Especially, it was investigated if the more detailed examination of residual quadrupolar interaction effects enables further analysis of the observed 23 Na MRI signal increase in MS patients., Materials and Methods: 23 Na MRI with a 7 T MR system was performed on 21 HC and 50 MS patients covering all MS subtypes (25 patients with relapsing-remitting MS, 14 patients with secondary progressive MS, and 11 patients with primary progressive MS) using 2 different 23 Na pulse sequences for quantification: a commonly used standard sequence (aTSC Std ) as well as a sequence with shorter excitation pulse length and lower flip angle for minimizing signal loss resulting from residual quadrupolar interactions (aTSC SP ). Apparent tissue sodium concentration was determined using the same postprocessing pipeline including correction of the receive profile of the radiofrequency coil, partial volume correction, and relaxation correction. Spin dynamic simulations of spin-3/2 nuclei were performed to aid in the understanding of the measurement results and to get deeper insight in the underlying mechanisms., Results: In normal-appearing white matter (NAWM) of HC and all MS subtypes, the aTSC SP values were approximately 20% higher than the aTSC Std values ( P < 0.001). In addition, the ratio aTSC SP /aTSC Std was significantly higher in NAWM than in normal-appearing gray matter (NAGM) for all subject cohorts ( P < 0.002). In NAWM, aTSC Std values were significantly higher in primary progressive MS compared with HC ( P = 0.01) as well as relapsing-remitting MS ( P = 0.03). However, in contrast, no significant differences between the subject cohorts were found for aTSC SP . Spin simulations assuming the occurrence of residual quadrupolar interaction in NAWM were in good accordance with the measurement results, in particular, the ratio aTSC SP /aTSC Std in NAWM and NAGM., Conclusions: Our results showed that residual quadrupolar interactions in white matter regions of the human brain have an influence on aTSC quantification and therefore must be considered, especially in pathologies with expected microstructural changes such as loss of myelin in MS. Furthermore, the more detailed examination of residual quadrupolar interactions may lead to a better understanding of the pathologies themselves., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Many female people with multiple sclerosis (pwMS) are in childbearing age; however, only few data exist about the situation of breastfeeding in pwMS. Objective: Our study analyzed breastfeeding rate and duration, reasons for weaning, and the impact of disease severity on successful breastfeeding in pwMS. Methods: The study included pwMS giving birth within 3 years before study participation. Data were collected by structured questionnaire. Results: Compared to published data, we found a significant difference ( p  = 0.0007) between the nursing rate in the general population (96.6%) and females with MS (85.9%). However, a higher rate of exclusive breastfeeding could be observed in our study population for 5-6 months in 40.6% of pwMS versus 9% for 6 months in the general population. In contrast, total breastfeeding duration in our study population was shorter (18.8% for 11-12 months) than in the general population (41.1% for 12 months). Reasons for weaning were predominantly (68.7%) related to breastfeeding barriers based on MS. No significant impact of prepartum or postpartum education on the breastfeeding rate could be observed. Prepartum relapse rate and prepartum disease-modifying drugs had no effect on breastfeeding success. Conclusion: Our survey provides an insight into the situation of breastfeeding in pwMS in Germany.

Apparent tissue sodium concentrations (aTSCs) determined by 23 Na brain magnetic resonance imaging (MRI) have the potential to serve as a biomarker in pathologies such as multiple sclerosis (MS). However, the quantification is hindered by the intrinsically low signal-to-noise ratio of 23 Na MRI. The purpose of this study was to improve the accuracy and reliability of quantitative 23 Na brain MRI by implementing a dedicated postprocessing pipeline and to evaluate the applicability of the developed approach for the examination of MS patients. 23 Na brain MRI measurements of 13 healthy volunteers and 17 patients with secondary progressive multiple sclerosis (SPMS) were performed at 7 T using a dual-tuned 23 Na/ 1 H birdcage coil with a receive-only 32-channel phased array. The aTSC values were determined for normal appearing white matter (NAWM) and normal appearing gray matter (NAGM) in healthy subjects and SPMS patients. Signal intensities were normalized using the mean cerebrospinal fluid (CSF) sodium concentration determined in 37 separate patients receiving a spinal tap for routine diagnostic purposes. Five volunteers underwent MRI examinations three times in a row to assess repeatability. Coefficients of variation (CoVs) were used to quantify the repeatability of the proposed method. aTSC values were compared regarding brain regions and subject cohort using the paired-samples Wilcoxon rank-sum test. Laboratory CSF sodium concentration did not differ significantly between patients without and with MS (p = 0.42). The proposed quantification workflow for 23 Na MRI was highly repeatable with CoVs averaged over all five volunteers of 1.9% ± 0.9% for NAWM and 2.2% ± 1.6% for NAGM. Average NAWM aTSC was significantly higher in patients with SPMS compared with the control group (p = 0.009). Average NAGM aTSC did not differ significantly between healthy volunteers and MS patients (p = 0.98). The proposed postprocessing pipeline shows high repeatability and the results can serve as a baseline for further studies establishing 23 Na brain MRI as a biomarker in diseases such as MS., (© 2022 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Purpose: To demonstrate direct imaging of the white matter ultrashort T 2 ∗ components at 7 Tesla using inversion recovery (IR)-enhanced ultrashort echo time (UTE) MRI. To investigate its characteristics, potentials and limitations, and to establish a clinical protocol., Material and Methods: The IR UTE technique suppresses long T 2 ∗ signals within white matter by using adiabatic inversion in combination with dual-echo difference imaging. Artifacts arising at 7 T from long T 2 relaxation times of white matter were then quantified. In 20 healthy volunteers, the UTE difference and fraction contrast were evaluated. Finally, in 6 patients with multiple sclerosis (MS), the performance of the technique was assessed.∗ scalp fat components were reduced by frequency shifting the IR pulse such that those frequencies were inverted likewise. For 8 healthy volunteers, the T 2 ∗ relaxation times of white matter were then quantified. In 20 healthy volunteers, the UTE difference and fraction contrast were evaluated. Finally, in 6 patients with multiple sclerosis (MS), the performance of the technique was assessed., Results: A frequency shift of -1.2 ppm of the IR pulse (i.e. towards the fat frequency) provided a good suppression of artifacts. With this, an ultrashort compartment of (68 ± 6) % with a T 2 ∗ time of (147 ± 58) μs was quantified with a chemical shift of (-3.6 ± 0.5) ppm from water. Within healthy volunteers' white matter, a stable ultrashort T 2 ∗ fraction contrast was calculated. For the MS patients, a significant fraction reduction in the identified lesions as well as in the normal-appearing white matter was observed., Conclusions: The quantification results indicate that the observed ultrashort components arise primarily from myelin tissue. Direct IR UTE imaging of the white matter ultrashort T 2 ∗ components is thus feasible at 7 T with high quantitative inter-subject repeatability and good detection of signal loss in MS., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Sodium enhancement has been demonstrated in multiple sclerosis (MS) lesions., Purpose: To investigate sodium MRI with and without an inversion recovery pulse in acute MS lesions in an MS relapse and during recovery., Study Type: Prospective., Subjects: Twenty-nine relapsing-remitting MS patients with an acute relapse were included., Field Strength/sequence: A 3D density-adapted radial sodium sequence at 3 T using a dual-tuned ( 23 Na/ 1 H) head coil., Assessment: Full-brain images of the tissue sodium concentration (TSC1, n = 29) and a sodium inversion recovery sequence (SIR1, n = 20) at the beginning of the anti-inflammatory therapy and on medium-term follow-up visits (days 27-99, n = 12 [TSC], n = 5 [SIR]) were measured. Regions of interest (RoIs) with contrast enhancement (T 1 CE+) and without change in T1-weighted imaging (FL + T1n) were normalized (nTSC and nSIR). To gain insight on the origin of the TSC enhancement at time point 1, it is investigated whether the nTSC enhancement of the lesions is accompanied by a change of the respective nSIR. Potential prognostic value of nSIR1 is examined referring to the nTSC progression. STATISTICAL TESTS: nTSC and nSIR were compared regarding the type of lesion and the time point using a one-way ANOVA. Pearson's correlation coefficient was calculated for nTSC over nSIR and for nTSC1-nTSC2 over nSIR1. A P-value <0.05 was considered statistically significant., Results: At the first measurement, all lesion types showed increased nTSC, while nSIR was decreased in the FL + T 1 n and the T 1 CE+ lesions in comparison to the normal-appearing white matter. For acute lesions, the difference between nTSC at baseline and nTSC at time point 2 showed a significant correlation with the baseline nSIR., Data Conclusion: At time point 1, nTSC is increased, while nSIR is unchanged or decreased in the lesions. The mean sodium IR signal at baseline correlates with recovery or progression of an acute lesion., Evidence Level: 2 TECHNICAL EFFICACY: Stage 4., (© 2021 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC. on behalf of International Society for Magnetic Resonance in Medicine.)

Novel MRI techniques allow a noninvasive quantification of tissue sodium and reveal the skin as a prominent compartment of sodium storage in health and disease. Since multiple sclerosis (MS) immunopathology is initiated in the periphery and increased sodium concentrations induce proinflammatory immune cells, the skin represents a promising compartment linking high sodium concentrations and MS immunopathology. We used a 7-T sodium MRI ( 23 Na-MRI) and inductively coupled plasma mass spectrometry to investigate the skin sodium content in two mouse models of MS. We additionally performed 3-T 23 Na-MRI of calf skin and muscles in 29 male relapsing-remitting MS (RRMS) patients and 29 matched healthy controls. Demographic and clinical information was collected from interviews, and disease activity was assessed by expanded disability status scale scoring. 23 Na-MRI and chemical analysis demonstrated a significantly increased sodium content in the skin during experimental autoimmune encephalomyelitis independent of active immunization. In male patients with RRMS, 23 Na-MRI demonstrated a higher sodium signal in the area of the skin compared to age- and biological sex-matched healthy controls with higher sodium, predicting future disease activity in cranial MRI. In both studies, the sodium enrichment was specific to the skin, as we found no alterations of sodium signals in the muscle or other tissues. Our data add to the recently identified importance of the skin as a storage compartment of sodium and may further represent an important organ for future investigations on salt as a proinflammatory agent driving autoimmune neuroinflammation such as that in MS., Competing Interests: The authors declare no competing interest.

Background: Pivotal trials showed good clinical efficiency of the monoclonal antibody ocrelizumab while being well tolerated and manageable in multiple sclerosis (MS). However, data on adverse events in everyday practice are scarce. Hence, our study aims at investigating short-term tolerability of ocrelizumab in a "real-world" setting., Methods: In this retrospective cohort study, data of 128 (86 relapsing-remitting, 42 progressive) MS patients at initiation of ocrelizumab were analyzed at the MS center of the University of Erlangen, Germany. Additionally, follow-up data of 68 patients at 6-months retreatment were analyzed. Structured phone interviews were applied after ocrelizumab initiation to report undocumented side effects., Results: Patients predominantly switched from monoclonal antibodies (46%), orals (20%), injectables (10%), steroids or immunosuppressants (each 8%), with a mean interval of 9.0 months after the last application of the previous immunotherapy. Applying a combined premedication with steroids, antihistamines and antipyretics for >90% of patients, ocrelizumab treatment was well tolerated and mainly comprised mild (n = 59/128 at initiation, n = 5/68 at 6 months retreatment) and rarely moderate (n = 7/128 at initiation, n = 2/68 at 6 months) side effects. Predominantly mild infusion related reactions (IRR) were reported with a declining percentage over the follow-up applications. Infections occurred rarely. No severe side effects were observed. Secondary, treatment appeared efficient when looking at clinical surrogates of stable disease., Discussion: Our study delineates good short-term tolerability of ocrelizumab in a miscellaneous "real-world" MS cohort. Additional studies are warranted to confirm these beneficial findings and to reveal safety concerns in the longer-term follow-up., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: Bowel incontinence in multiple sclerosis might be associated with specific lesion sites. This study intended to determine associations between bowel incontinence and cerebral multiple sclerosis lesions using a voxel-wise lesion symptom mapping analysis., Methods: We conducted a retrospective study of multiple sclerosis patients with self-reported bowel incontinence and matched controls. Lesions were manually outlined on T2-weighted MRI scans and transformed into stereotaxic space. We performed a voxel-wise subtraction analysis subtracting the lesion overlap of patients without from patients with bowel incontinence. Finally, we compared the absence or presence of bowel incontinence between patients with and without lesions in a given voxel using the Liebermeister test., Results: A total of 51 patients were included in the study. The analysis yielded associations between bowel incontinence and lesions in the supramarginal gyrus of the left secondary somatosensory cortex and another lesion cluster in the right parahippocampal gyrus and amygdala., Conclusions: Our analysis indicates associations between bowel incontinence and lesions in the left supramarginal gyral area contributing to integrating anorectal-visceral sensation and in the right parahippocampal gyrus and amygdala contributing to generating visceral autonomic arousal states. Moreover, our results suggest left hemispheric dominance of sensory visceral integration, while limbic areas of the right hemisphere seem to contribute to the autonomic component of the defecation process. A limitation of our study is the retrospective evaluation of the bowel incontinence status based on medical records. Further research should evaluate the bowel incontinence status in multiple sclerosis patients prospectively to overcome the limitations of the current study., (© 2018 by the American Society of Neuroimaging.)

Secondary paroxysmal dyskinesia is a rare but life-quality-compromising symptom in multiple sclerosis (MS) and might be associated with particular MS lesions. The present study intended to determine associations between paroxysmal dyskinesia and the MS-associated lesion site using a voxelwise lesion analysis. We conducted a retrospective study and sought MS patients with documented paroxysmal dyskinesia and controls without paroxysmal dyskinesia matched for age, disease severity, and disease duration in a local database. The MS lesions were analysed on T2-weighted magnetic resonance imaging scans (1.5 or 3 T), manually outlined, and transformed into stereotaxic space. We determined the lesion overlap and compared the absence or presence of paroxysmal dyskinesia voxelwise between patients with and without lesions in a given voxel using the Liebermeister test with 4000 permutations. From 15,869 MS patient records screened, we identified 25 patients with paroxysmal dyskinesia. The voxelwise analysis in 22 subjects yielded associations between paroxysmal dyskinesia and MS lesions in the internal capsule, the basal ganglia, and another prominent lesion cluster in the posterior periventricular white matter. Our voxelwise analysis shows associations between paroxysmal dyskinesia and MS lesions in the internal capsule and basal ganglia, areas contributing to motor sequence programming. This association in another lesion site located in the posterior thalamic radiation suggests that lesions in subcortical sensory pathways may also contribute to paroxysmal dyskinesia in MS.

Background: Chronic inflammatory demyelinating diseases of the CNS typically show a limited lesion size. However, extended lesions may appear with an atypical configuration. Large lesions with a diameter>2cm accompanied by tumor-like edema are entitled "tumefactive" and may occur in multiple sclerosis (MS) and other demyelinating diseases. Historically, differential diagnosis often requires histological analysis. Therefore, advanced imaging techniques are warranted to allow for a precise non-invasive diagnosis. Cerebral sodium ( 23 Na) MRI was recently described as a new method to investigate in vivo sodium accumulation. Indicating extended sodium levels in MS lesions, 23 Na MRI is a promising differential diagnostic tool further elucidating the role of sodium in demyelinating lesions., Methods: Repetitive 23 Na MRI measurements in a MS patient with a tumefactive demyelinating lesion providing insight into the medium-term course of cerebral sodium levels., Results and Conclusion: 23 Na MRI depicts persistent lesional sodium accumulation after anti-inflammatory treatment and provides the opportunity of a non-invasive, in vivo analysis of sodium levels in inflammatory CNS lesions without need for contrast enhancing media. As a result of the extended dimension, tumefactive lesions may have an appropriate size for the analysis of inflammatory demyelination by 23 Na MRI with sufficient resolution., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Purpose: Some 3%-10% of patients with multiple sclerosis (MS) experience disease onset before the age of 18 years ('early' onset MS, EOMS). Optical coherence tomography is a non-invasive method to measure retinal nerve fibre layer thickness (RNFLT) and total macular volume (TMV) and may be useful to differentiate axonal and neuronal damage in the retina of patients with a history of EOMS. Here RNFLT and TMV in EOMS patients after a mean disease duration of 11.6 years were compared with patients with age- or disease-duration-matched later onset MS (LOMS) and healthy controls (HCs)., Methods: In this observational cross-sectional study at two German academic MS centres, RNFLT and TMV were measured by spectral-domain optical coherence tomography in 32 HCs, 36 EOMS (mean age at onset 15.5 ± 2.0 years) and 58 LOMS patients., Results: In comparison with HCs, EOMS patients displayed a significant reduction of RNFLT and TMV independently of a history of optic neuritis. In particular, RNFLT loss in EOMS was similar to that in LOMS and TMV loss was slightly higher compared with disease-duration-matched LOMS. In a generalized estimating model, the EOMS group also displayed a similar correlation between disease duration and RNFLT or TMV loss to LOMS patients., Conclusions: These data argue for a significant amount of axonal and neuronal damage in the retina of EOMS patients and may provide a structural basis for the observation that EOMS patients reach states of irreversible disability at a younger age than patients with LOMS., (© 2014 EAN.)