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Background Patients with neuromyelitis optica spectrum disorder (NMOSD) are often seropositive for antibodies against aquaporin-4 (AQP4). The importance of MRI monitoring in this disease requires evaluation. Purpose To profile MRI features from a large international cohort with AQP4 immunoglobulin G (IgG)-seropositive NMOSD (from the Parallel MRI in NMOSD [PAMRINO] study) and to evaluate and confirm existing knowledge regarding the incidence, location, and longitudinal development of characteristic lesions in the central nervous system associated with AQP4-IgG-seropositive NMOSD. Materials and Methods In this retrospective study (from August 2016 to January 2019), MRI and clinical data were collected from 17 NMOSD expert sites in 11 countries across four continents. Clinical features and lesions identified at cross-sectional and longitudinal MRI were assessed. No formal statistical tests were used to compare observations; however, means, SDs, and 95% CIs are reported when evaluating lesion frequencies. Results Available T1-weighted and T2-weighted MRI scans in patients with AQP4-IgG-seropositive NMOSD ( n = 525) were read. Among the 525 patients, 320 underwent cerebral MRI examinations with T2-weighted hyperintense cerebral (264 of 320; 82.5%), cerebellar (44 of 320; 13.8%), and brainstem (158 of 321 [49.2%], including one lesion observed at cervical spinal cord [SC] MRI) lesions. Lesions in the optic nerves, analyzed from 152 MRI examinations, were mainly found in the central (81 of 92; 88%) and posterior (79 of 92; 86%) sections (bilaterally in 39 of 92; 42%). Longitudinally extensive transverse myelitis was the predominant SC lesion pattern (upper compartment from 322 MRI examinations, 133 of 210 [63.3%]; and lower compartment from 301 MRI examinations, 149 of 212 [70.3%]). However, nonlongitudinal extensive transverse myelitis lesions were also observed frequently (105 of 210; 50.0%) in the cervical SC. Clinical data ( n = 349; mean age, 44 years ± 14 [SD]; 202 female patients) and acute lesions at contrast-enhanced (CE) MRI ( n = 58, performed within 30 days of the last attack) were evaluated. CE lesions were detected in the cerebrum (eight of 13; 62%), optic nerves (14 of 19; 74%), or chiasm (three of four; 75%) within 15 days of any relapse. In the upper SC (29 of 44; 66%), CE lesions were frequently observed up to 20 days after a clinical myelitis event. Conclusion A high incidence of abnormal brain MRI examinations and nonlongitudinal extensive SC lesions was found in patients in PAMRINO with AQP4-IgG-seropositive NMOSD. © RSNA, 2024 Supplemental material is available for this article.

Background: Currently, there is no evidence-based definition of attacks in neuromyelitis optica spectrum disorders (NMOSD). However, to allow their stringent use as valid endpoints, recent phase III trials in NMOSD defined criteria and adjudication of these events in context of these trials. The objective of this study was to investigate diagnostic procedures currently used in routine adjudication of suspected attacks in NMOSD, and to assess whether the standardized attack-criteria from two pivotal trials may be feasible in routine clinical care., Methods: Four global clinical networks were surveyed using an online questionnaire: NEMOS (Neuromyelitis Optica Study Group), IMSVISUAL (International Multiple Sclerosis Visual System Consortium), GJCF-ICC (Guthy Jackson Charitable Foundation-International Clinical Consortium) and NOMADMUS (Devic's neuromyelitis optica and related neurological disorders study group)., Results: Seventy-eight responses were received from September 2018 to February 2019. Median annual number of patients seen with suspected attacks was 10 (range 2-130). Immediate access to MRI was reported by 59.0% of all participants and the majority performs an MRI for new patients with a myelitis, optic neuritis or other symptoms. In patients with established NMOSD diagnosis presenting during routine clinical visits only 10.5% or 9.2% always perform a brain or spinal cord MRI, respectively. Digital records of patients' visits are kept by 98.7% of all participants and 88.5% have direct access to case history. An expert neurological examination is performed for 94.9% of participants reported to perform an expert neurological examination in patients with acute attacs, while only 30.8% seem to perform the assessments according to the Neurostatus-Expanded Disability Status Scale (EDSS) definitions.. The Sakura Star study criteria which are based solely on clinical assessment could be feasible in routine care, provided that more centers use the Neurostatus-EDSS, while only 9% of participants fulfill all requirements for adjudication of the N-Momentum study criteria., Conclusions: The high percentage of centers using digital records is encouraging. However, routine adjudication of clinical events in NMOSD seems highly heterogeneous. MRI is the mainstay in the majority of queried centers, but its immediate availability is limited. Only a minority of centers are equipped for trial-grade classification of attacks, if this is not solely clinically based. Thus, standard and feasible guidelines for attack adjudication are urgently needed to standardize routine care, optimize future clinical trials and allow studying long-term safety and efficacy of newly approved drugs in phase IV trials., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Machine learning-based imaging diagnostics has recently reached or even surpassed the level of clinical experts in several clinical domains. However, classification decisions of a trained machine learning system are typically non-transparent, a major hindrance for clinical integration, error tracking or knowledge discovery. In this study, we present a transparent deep learning framework relying on 3D convolutional neural networks (CNNs) and layer-wise relevance propagation (LRP) for diagnosing multiple sclerosis (MS), the most widespread autoimmune neuroinflammatory disease. MS is commonly diagnosed utilizing a combination of clinical presentation and conventional magnetic resonance imaging (MRI), specifically the occurrence and presentation of white matter lesions in T2-weighted images. We hypothesized that using LRP in a naive predictive model would enable us to uncover relevant image features that a trained CNN uses for decision-making. Since imaging markers in MS are well-established this would enable us to validate the respective CNN model. First, we pre-trained a CNN on MRI data from the Alzheimer's Disease Neuroimaging Initiative (n = 921), afterwards specializing the CNN to discriminate between MS patients (n = 76) and healthy controls (n = 71). Using LRP, we then produced a heatmap for each subject in the holdout set depicting the voxel-wise relevance for a particular classification decision. The resulting CNN model resulted in a balanced accuracy of 87.04% and an area under the curve of 96.08% in a receiver operating characteristic curve. The subsequent LRP visualization revealed that the CNN model focuses indeed on individual lesions, but also incorporates additional information such as lesion location, non-lesional white matter or gray matter areas such as the thalamus, which are established conventional and advanced MRI markers in MS. We conclude that LRP and the proposed framework have the capability to make diagnostic decisions of CNN models transparent, which could serve to justify classification decisions for clinical review, verify diagnosis-relevant features and potentially gather new disease knowledge., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to evaluate integrated (18)F-FDG PET/MRI as a one-stop diagnostic procedure in the assessment of (active) idiopathic retroperitoneal fibrosis (RPF) METHODS: A total of 22 examinations comprising a PET/CT scan followed by a PET/MRI scan in 17 patients (13 men, 4 women, age 58 ± 11 years) with histopathologically confirmed RPF at diagnosis or during follow-up under steroid therapy were analysed in correlation with laboratory inflammation markers (ESR, CRP). The patient cohort was subdivided into two groups: 6 examinations in untreated and 16 in treated patients. Tissue formations in typically periaortic localization suggestive of RPF were visually and quantitatively evaluated. The PET analysis included the assessment of SUVmax and a qualitative score for FDG uptake in RPF tissue in relation to the uptake in the liver. MRI analysis included evaluation of the T2-weighted image signal intensity, contrast enhancement and diffusion restriction (ADC values). Mean values were compared using the Mann-Whitney U test. ADC, SUVmax and ESR values were correlated using Pearson's correlation., Results: MRI analysis revealed restricted diffusion in 100 % and 56 %, hyperintense T2 signal in 100 % and 31 %, and contrast enhancement in the periaortic tissue formation suggestive of RPF in 100 % and 62.5 % in the untreated and treated patients, respectively. In the qualitative and quantitative PET analysis, statistically significant differences were found for mean FDG uptake scores (2.5 ± 0.8 in untreated patients and 1.1 ± 0.9 in treated patients) and mean SUVmax (7.8 ± 3.5 and 4.1 ± 2.2, respectively). A strong correlation was found between the ADC values and SUVmax (Pearson r   -0.65, P = 0.0019), and between ESR and CRP values and SUVmax (both r = 0.45, P = 0.061)., Conclusion: Integrated (18)F-FDG PET/MRI shows high diagnostic potential as a one-stop diagnostic procedure for the assessment of (active) RPF providing multiparametric supportive information.

We analysed the infrarenal aortic morphology by abdominal MR-examinations of 47 RPF patients compared to a control group. A significant larger aortic calibre and higher rates of infrarenal dilatation in male RPF patients were observed. The larger aortic diameter in male RPF patients may be due to periaortic inflammation with resulting aortic ectasia and supports the classification of RPF into the spectrum of chronic periaortitis.

Background: Damage to venules in multiple sclerosis was first described decades ago. Today, ultrahigh magnetic field strength T2*-weighted magnetic resonance imaging (MRI) techniques depict very small cerebral veins in vivo with great anatomical detail., Objective: We aimed to investigate alterations of periventricular small blood vessel appearance in relation to T2 lesion count and distribution in multiple sclerosis and clinically isolated syndrome in comparison with healthy control subjects at 7 Tesla MRI., Methods: We investigated 38 patients (including 16 with early multiple sclerosis and seven with clinically isolated syndrome) and 22 matched healthy controls at 7 Tesla. The protocol included T2*-weighted Fast Low Angle Shot, and T2-weighted Turbo Inversion Recovery Magnitude sequences. We quantified periventricular venous density by a novel region-of-interest-based algorithm, expressing the ratio of 'veins per region-of-interest' as well as of 'periventricular vascular area'., Results: Our study revealed significantly decreased venous density in multiple sclerosis patients compared with healthy controls. Venous alterations were already detectable in clinically isolated syndrome and early multiple sclerosis, although to a smaller extent. Venous density correlated inversely with periventricular and whole-brain T2 lesion count. Furthermore, we found no indication for cerebral venous congestion in multiple sclerosis., Conclusion: High spatially resolving anatomical T2*-weighted MRI revealed vascular alterations in early stages of multiple sclerosis, presumably as a part of widespread haemodynamic and metabolic alterations.

Background and purpose: Thinning of the retinal combined ganglion cell and inner plexiform layer (GCIP) as measured by optical coherence tomography (OCT) is a common finding in patients with multiple sclerosis. This study aimed to investigate whether a single retinal OCT analysis allows prediction of future disease activity after a first demyelinating event. Methods: This observational cohort study included 201 patients with recently diagnosed clinically isolated syndrome or relapsing–remitting multiple sclerosis from two German tertiary referral centers. Individuals underwent neurological examination, magnetic resonance imaging, and OCT at baseline and at yearly follow‐up visits. Results: Patients were included at a median disease duration of 2.0 months. During a median follow‐up of 59 (interquartile range = 43–71) months, 82% of patients had ongoing disease activity as demonstrated by failing the no evidence of disease activity 3 (NEDA‐3) criteria, and 19% presented with confirmed disability worsening. A GCIP threshold of ≤77 μm at baseline identified patients with a high risk for NEDA‐3 failure (hazard ratio [HR] = 1.7, 95% confidence interval [CI] = 1.1–2.8, p = 0.04), and GCIP measures of ≤69 μm predicted disability worsening (HR = 2.2, 95% CI = 1.2–4.3, p = 0.01). Higher rates of annualized GCIP loss increased the risk for disability worsening (HR = 2.5 per 1 μm/year increase of GCIP loss, p = 0.03). Conclusions: Ganglion cell thickness as measured by OCT after the initial manifestation of multiple sclerosis may allow early risk stratification as to future disease activity and progression. [ABSTRACT FROM AUTHOR]

Background: Serum neurofilament light (sNfL) chain is a promising biomarker reflecting neuro-axonal injury in multiple sclerosis (MS). However, the ability of sNfL to predict outcomes in real-world MS cohorts requires further validation. Objective: The aim of the study is to investigate the associations of sNfL concentration, magnetic resonance imaging (MRI) and retinal optical coherence tomography (OCT) markers with disease worsening in a longitudinal European multicentre MS cohort. Methods: MS patients (n = 309) were prospectively enrolled at four centres and re-examined after 2 years (n = 226). NfL concentration was measured by single molecule array assay in serum. The patients' phenotypes were thoroughly characterized with clinical examination, retinal OCT and MRI brain scans. The primary outcome was disease worsening at median 2-year follow-up. Results: Patients with high sNfL concentrations (⩾8 pg/mL) at baseline had increased risk of disease worsening at median 2-year follow-up (odds ratio (95% confidence interval) = 2.8 (1.5–5.3), p = 0.001). We found no significant associations of MRI or OCT measures at baseline with risk of disease worsening. Conclusion: Serum NfL concentration was the only factor associated with disease worsening, indicating that sNfL is a useful biomarker in MS that might be relevant in a clinical setting. [ABSTRACT FROM AUTHOR]

Background: Cross-sectional studies suggest normal appearing white matter (NAWM) integrity loss may lead to cortical atrophy in late-stage relapsing-remitting multiple sclerosis (MS). Objective: To investigate the relationship between NAWM integrity and cortical thickness from first clinical presentation longitudinally. Methods: NAWM integrity and cortical thickness were assessed with 3T magnetic resonance imaging (MRI) in 102 patients with clinically isolated syndrome or early MS (33.2 (20.1–60.1) years old, 68% female) from first clinical presentation over 2.8 ± 1.6 years. Fifty healthy controls (HCs) matched for age and sex were included. NAWM integrity was evaluated using the standardized T1w/T2w ratio (sT1w/T2w). The association between sT1w/T2w and cortical thickness was assessed using linear mixed models. The effect of disease activity was investigated using the No Evidence of Disease Activity (NEDA-3) criteria. Results: At baseline, sT1w/T2w (p = 0.152) and cortical thickness (p = 0.489) did not differ from HCs. Longitudinally, decreasing sT1w/T2w was associated with cortical thickness and increasing lesion burden (marginal R 2 = 0.061). The association was modulated by failing NEDA-3 (marginal R 2 = 0.097). Conclusion: sT1w/T2w may be a useful MRI biomarker for early MS, detecting relevant NAWM damage over time using conventional MRI scans, although with less sensitivity compared to quantitative measures. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to use a novel MRI contrast, the standardized T1-weighted/T2-weighted (sT1w/T2w) ratio, to assess damage of the white matter and gray matter in multiple system atrophy (MSA). Furthermore, this study investigated whether the sT1w/T2w ratio was associated with cognitive impairment in MSA. Methods: The white matter and gray matter sT1w/T2w ratio of 37 MSA patients and 19 healthy controls were measured. Correlation analyses were used to evaluate the relationship between sT1w/T2w ratio values and clinical variables, and a multivariate analysis was used to identify independent factors associated with cognitive impairment in MSA. Results: MSA patients showed a higher white matter sT1w/T2w ratio value than controls (p < 0.001), and the white matter sT1w/T2w ratio value was significantly correlated with the International Cooperative Ataxia Rating Scale score (r = 0.377, p = 0.021) and the Addenbrooke's cognitive examination III score (r = −0.438, p = 0.007). Cognitively impaired MSA patients had a significantly higher white matter sT1w/T2w ratio value than cognitively preserved MSA patients (p = 0.010), and the multiple logistic regression analysis revealed that the median white matter sT1w/T2w ratio value was independently associated with cognitive impairment in MSA. Conclusion: The sT1w/T2w ratio is sensitive to degenerative changes in the white matter that is associated with cognitive ability in MSA patients. [ABSTRACT FROM AUTHOR]

Objectives: Genetic variant classification is a challenge in rare adult‐onset disorders as in SCA‐PRKCG (prior spinocerebellar ataxia type 14) with mostly private conventional mutations and nonspecific phenotype. We here propose a refined approach for clinicogenetic diagnosis by including protein modeling and provide for confirmed SCA‐PRKCG a comprehensive phenotype description from a German multi‐center cohort, including standardized 3D MR imaging. Methods: This cross‐sectional study prospectively obtained neurological, neuropsychological, and brain imaging data in 33 PRKCG variant carriers. Protein modeling was added as a classification criterion in variants of uncertain significance (VUS). Results: Our sample included 25 cases confirmed as SCA‐PRKCG (14 variants, thereof seven novel variants) and eight carriers of variants assigned as VUS (four variants) or benign/likely benign (two variants). Phenotype in SCA‐PRKCG included slowly progressive ataxia (onset at 4–50 years), preceded in some by early‐onset nonprogressive symptoms. Ataxia was often combined with action myoclonus, dystonia, or mild cognitive‐affective disturbance. Inspection of brain MRI revealed nonprogressive cerebellar atrophy. As a novel finding, a previously not described T2 hyperintense dentate nucleus was seen in all SCA‐PRKCG cases but in none of the controls. Interpretation: In this largest cohort to date, SCA‐PRKCG was characterized as a slowly progressive cerebellar syndrome with some clinical and imaging features suggestive of a developmental disorder. The observed non‐ataxia movement disorders and cognitive‐affective disturbance may well be attributed to cerebellar pathology. Protein modeling emerged as a valuable diagnostic tool for variant classification and the newly described T2 hyperintense dentate sign could serve as a supportive diagnostic marker of SCA‐PRKCG. [ABSTRACT FROM AUTHOR]

Aims: To explore differences in advanced brain magnetic resonance imaging (MRI) characteristics between myelin oligodendrocyte (MOG) immunoglobulin (IgG) and aquaporin-4 (AQP4) IgG seropositive (+) neuromyelitis optica spectrum disorders (NMOSD). Methods: 33 AQP4-IgG and 18 MOG-IgG seropositive NMOSD patients and 61 healthy control (HC) subjects were included. All 112 participants were scanned with the same standardized MRI-protocol on a 3-Tesla MRI-scanner. Brain volume and diffusion tensor imaging (DTI) parameters were assessed. Results: MOG-IgG+ patients showed reduced parallel diffusivity within white matter tracts compared to HC whereas AQP4-IgG+ showed no significant brain parenchymal damage in DTI analysis. AQP4-IgG+ patients showed reduced whole brain volumes and reduced volumes of several deep gray matter structures compared to HC whereas MOG-IgG+ patients did not show reduced brain or deep gray matter volumes compared to HC. Conclusions: Microstructural brain parenchymal damage in MOG-IgG+ patients was more pronounced than in AQP4-IgG+ patients, compared with HC, whereas normalized brain volume reduction was more severe in AQP4-IgG+ patients. Longitudinal imaging studies are warranted to further investigate this trend in NMOSD. Our results suggest that MOG-IgG+ and AQP4-IgG+ NMOSD patients differ in cerebral MRI characteristics. Advanced MRI analysis did not help to differentiate between MOG-IgG+ and AQP4-IgG+ patients in our study. [ABSTRACT FROM AUTHOR]

Background: Brain lesions with a hypointense ring or core were described in multiple sclerosis on susceptibility weighted imaging. Objective: The purpose of this study was to study the evolution and prognostic relevance of susceptibility weighted imaging hypointense lesions in clinically isolated syndrome and early multiple sclerosis. Methods: Sixty-six early multiple sclerosis and clinically isolated syndrome patients were followed over a median period of 2.9 years (range 1.6-4.6 years) and underwent 3T magnetic resonance imaging including 3D susceptibility weighted imaging and T2-weighted fluid-attenuated inversion recovery. We assessed the presence of susceptibility weighted imaging hypointense core or ring lesions, and Expanded Disability Status Scale at baseline and follow-up. Results: Of 611 lesions at baseline, 64 (10.5%) had a susceptibility weighted imaging hypointense core, and 28 (4.6%) had a susceptibility weighted imaging hypointense ring. Hypointense ring lesions were larger (p<0.001) and more T1w hypointense (p=0.002) than others. During follow-up, hypointense core lesions became susceptibility weighted imaging isointense (52 lesions, 81%); few developed into hypointense ring lesions (two lesions, 3%). Hypointense ring lesions did not shrink on T2-weighted fluid-attenuated inversion recovery images (p=0.077, trend towards more enlargement compared to others), while hypointense core lesions more often shrunk in comparison to lesions without a hypo- intense core (p=0.002). The number of susceptibility weighted imaging hypointense ring lesions at baseline correlated with Expanded Disability Status Scale progression at follow-up (p=0.021, R=0.289). Conclusion: In our cohort of patients with clinically isolated syndrome or early multiple sclerosis, susceptibility weighted imaging hypointense ring lesions were only rarely detectable, but did not shrink and were associated with future disability progression. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica spectrum disorders (NMOSD) are mostly relapsing autoimmune inflammatory disorders of the central nervous system (CNS) with optic neuritis, myelitis, and brainstem syndromes as clinical hallmarks. With a reported prevalence of up to 70%, cognitive impairment is frequent, but often unrecognized and an insufficiently treated burden of the disease. The most common cognitive dysfunctions are decline in attention and memory performance. Magnetic resonance imaging can be used to access structural correlates of neuropsychological disorders. Cognitive impairment is not only a highly underestimated symptom in patients with NMOSD, but potentially also a clinical correlate of attack-independent changes in NMOSD, which are currently under debate. This article reviews cognitive impairment in NMOSD and discusses associations between structural changes of the CNS and cognitive deficits. [ABSTRACT FROM AUTHOR]

Background: Previous studies have postulated an association between dentate nucleus T1 hyperintensity and multiple sclerosis (MS)-related progressive neurodegeneration. Therefore, MS patients have been excluded from most studies investigating brain deposition of gadolinium-based contrast agents (GBCAs). Objective: To study the hypothesis that dentate nucleus T1 hyperintensity in MS patients is associated with GBCA administration. Methods: In a cohort of 97 MS patients, the dentate-to-pons signal intensity ratio (DPSIR) was calculated for 265 consecutive T1-weighted magnetic resonance (MR) scans (including sessions with and without the administration of GBCA). Patients exclusively received either gadopentetate dimeglumine (Gd-DTPA, linear) or gadobutrol (Gd-BT-DO3A, macrocyclic). Results: In patients receiving Gd-DTPA, DPSIR increased significantly between the first and the last scan (+0.009, p < 0.001), and following magnetic resonance imaging (MRI) with Gd-DTPA administration as compared to following an MRI without Gd-DTPA administration (+0.005 vs −0.001; p = 0.022). Additionally, there was a positive linear relationship between the number of Gd-DTPA administrations and the increase in DPSIR (p = 0.017). No DPSIR increase was observed after Gd-BT-DO3A administration. Conclusion: Dentate nucleus T1 hyperintensity in MS patients is associated with Gd-DTPA (but not Gd-BT-DO3A) administration, suggesting an alternative explanation for the association of T1 hyperintensity with disease duration and severity. [ABSTRACT FROM AUTHOR]

Objectives: Application of multifrequency magnetic resonance elastography (MMRE) of the brain parenchyma in patients with neuromyelitis optica spectrum disorder (NMOSD) compared to age matched healthy controls (HC).Methods: 15 NMOSD patients and 17 age- and gender-matched HC were examined using MMRE. Two three-dimensional viscoelastic parameter maps, the magnitude |G*| and phase angle φ of the complex shear modulus were reconstructed by simultaneous inversion of full wave-field data in 1.9-mm isotropic resolution at 7 harmonic drive frequencies from 30 to 60 Hz.Results: In NMOSD patients, a significant reduction of |G*| was observed within the white matter fraction (p = 0.017), predominantly within the thalamic regions (p = 0.003), compared to HC. These parameters exceeded the reduction in brain volume measured in patients versus HC (p = 0.02 whole-brain volume reduction). Volumetric differences in white matter fraction and the thalami were not detectable between patients and HC. However, phase angle φ was decreased in patients within the white matter (p = 0.03) and both thalamic regions (p = 0.044).Conclusions: MMRE reveals global tissue degeneration with accelerated softening of the brain parenchyma in patients with NMOSD. The predominant reduction of stiffness is found within the thalamic region and related white matter tracts, presumably reflecting Wallerian degeneration.Key Points: • Magnetic resonance elastography reveals diffuse cerebral tissue changes in patients with NMOSD. • Premature tissue softening in NMOSD patients indicates tissue degeneration. • Hypothesis of a widespread cerebral neurodegeneration in form of diffuse tissue alteration. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association of Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) and viral capsid antigen (VCA) immunoglobulin (Ig)G antibodies in serum as well as EBV DNA load in saliva with radiological and clinical disease activity in patients with clinically isolated syndrome (CIS) and early relapsing-remitting MS (RRMS). Methods: EBNA-1 and VCA immunoglobulin (Ig)G antibodies were determined in serum of 100 patients with CIS/early RRMS and 60 healthy controls. EBV DNA load was measured in saliva of 48 patients and 50 controls. Patients underwent clinical assessment with the Expanded Disability Status Scale (EDSS) and 3 Tesla magnetic resonance imaging at baseline and after a median of 20 months of follow-up (n = 63 for MRI, n = 71 for EDSS). The association of EBV parameters with occurrence of a second relapse, indicating conversion to clinically definite MS (CDMS), was evaluated over a median of 35 months of follow-up after the first clinical event (n = 89). Results: EBNA-1 IgG antibody frequency (p = 0.00005) and EBNA-1 and VCA IgG antibody levels (p<0.0001 for both) were higher in patients than in controls. EBV DNA load in saliva did not differ between groups. Neither EBV antibody levels nor DNA load in saliva were associated with baseline or follow-up number or volume of T2-weighted (T2w) or contrast enhancing lesions, number of Barkhof criteria or the EDSS, or with the number of new T2w lesions, T2w lesion volume change or EDSS change on follow-up. Likewise, levels of EBV IgG antibodies in serum and DNA load in saliva were not associated with conversion to CDMS. Conclusions: While these findings confirm the association of EBV infection with early MS, neither EBNA-1 nor VCA IgG antibodies in serum nor EBV DNA load in saliva were associated with radiological or clinical disease activity in patients with CIS/early RRMS. These data are compatible with the concept that EBV may be a trigger for MS acting very early during the development of the disease. [ABSTRACT FROM AUTHOR]

Background: The PMP22 gene encodes a protein integral to peripheral myelin. Its deletion leads to hereditary neuropathy with liability to pressure palsies (HNPP). PMP22 is not expressed in the adult central nervous system, but previous studies suggest a role in CNS myelin development. The objective of this study was to identify potential structural and functional alterations in the afferent visual system in HNPP patients. Methods: Twenty HNPP patients and 18 matched healthy controls (HC) were recruited in a cross-sectional study. Participants underwent neurological examination including visual acuity, visual evoked potential (VEP) examination, optical coherence tomography (OCT), and magnetic resonance imaging with calculation of brain atrophy, regarding grey and white matter, and voxel based morphometry (VBM), in addition answered the National Eye Institute’s 39-item Visual Functioning Questionnaire (NEI-VFQ). Thirteen patients and 6 HC were additionally examined with magnetic resonance spectroscopy (MRS). Results: All patients had normal visual acuity, but reported reduced peripheral vision in comparison to HC in the NEI-VFQ (p = 0.036). VEP latency was prolonged in patients (P100 = 103.7±5.7 ms) in comparison to healthy subjects (P100 = 99.7±4.2 ms, p = 0.007). In OCT, peripapillary retinal nerve fiber layer thickness RNFL was decreased in the nasal sector (90.0±15.5 vs. 101.8±16.5, p = 0.013), and lower nasal sector RNFL correlated with prolonged VEP latency (Rho = -0.405, p = 0.012). MRS revealed reduced tNAA (731.4±45.4 vs. 814.9±62.1, p = 0.017) and tCr (373.8±22.2 vs. 418.7±31.1, p = 0.002) in the visual cortex in patients vs. HC. Whole brain volume, grey and white matter volume, VBM and metabolites in a MRS sensory cortex control voxel did not differ significantly between patients and HC. Conclusion: PMP22 deletion leads to functional, metabolic and macro-structural alterations in the afferent visual system of HNPP patients. Our data suggest a functional relevance of these changes for peripheral vision, which warrants further investigation and confirmation. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate integrated F-FDG PET/MRI as a one-stop diagnostic procedure in the assessment of (active) idiopathic retroperitoneal fibrosis (RPF) Methods: A total of 22 examinations comprising a PET/CT scan followed by a PET/MRI scan in 17 patients (13 men, 4 women, age 58 ± 11 years) with histopathologically confirmed RPF at diagnosis or during follow-up under steroid therapy were analysed in correlation with laboratory inflammation markers (ESR, CRP). The patient cohort was subdivided into two groups: 6 examinations in untreated and 16 in treated patients. Tissue formations in typically periaortic localization suggestive of RPF were visually and quantitatively evaluated. The PET analysis included the assessment of SUVmax and a qualitative score for FDG uptake in RPF tissue in relation to the uptake in the liver. MRI analysis included evaluation of the T2-weighted image signal intensity, contrast enhancement and diffusion restriction (ADC values). Mean values were compared using the Mann-Whitney U test. ADC, SUVmax and ESR values were correlated using Pearson's correlation. Results: MRI analysis revealed restricted diffusion in 100 % and 56 %, hyperintense T2 signal in 100 % and 31 %, and contrast enhancement in the periaortic tissue formation suggestive of RPF in 100 % and 62.5 % in the untreated and treated patients, respectively. In the qualitative and quantitative PET analysis, statistically significant differences were found for mean FDG uptake scores (2.5 ± 0.8 in untreated patients and 1.1 ± 0.9 in treated patients) and mean SUVmax (7.8 ± 3.5 and 4.1 ± 2.2, respectively). A strong correlation was found between the ADC values and SUVmax (Pearson r −0.65, P = 0.0019), and between ESR and CRP values and SUVmax (both r = 0.45, P = 0.061). Conclusion: Integrated F-FDG PET/MRI shows high diagnostic potential as a one-stop diagnostic procedure for the assessment of (active) RPF providing multiparametric supportive information. [ABSTRACT FROM AUTHOR]

PURPOSE We aimed to evaluate diffusion-weighted imaging (DWI) findings in patients with treated and untreated retroperitoneal fibrosis (RPF). METHODS We analyzed magnetic resonance imaging examinations of 44 RPF patients (36 male, 8 female), of which 15 were untreated and 29 were under therapy. Qualitative DWI and T1 postcontrast signal intensities and the largest perivascular extent of RPF were compared between treated and untreated groups and correlated to erythrocyte sedimentation rate and C-reactive protein values. Quantitative DWI signal intensities and apparent-diffusion-coefficients were calculated in regions-of-interest, together with a relative index between signal intensities of RPF and psoas muscle in 15 untreated patients and 14 patients under treatment with remaining perivascular fibrosis of more than 5 mm. RESULTS The extent of RPF in untreated patients was significantly larger compared with the extent of RPF in treated patients (P < 0.0001). DWI signal intensities were significantly higher in untreated patients than in patients under therapy (mean, 27 s/mm2 vs. 20 s/mm2; P = 0.009). The calculated DWI-index was significantly higher in untreated patients than in patients under therapy (P = 0.003). CONCLUSION Our data show significant differences in the DWI findings (b800 signal intensities and relative DWI-index) of patients with treated and untreated RPF. DWI is a promising technique in the assessment of disease activity and the selection of patients suitable for medical therapy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the therapeutic effect of tamoxifen monotherapy in patients with retroperitoneal fibrosis (RPF). Patients and Methods: From 2007 on, 31 patients with idiopathic RPF were treated with tamoxifen monotherapy. Follow-up investigations included magnetic resonance imaging, laboratory measurements, registration of side effects and changes or removal of ureteral stents. Data were stored in the Else Kröner-Fresenius Registry of Retroperitoneal Fibrosis. Results: 25 men and 6 women with a mean age of 56.6 years were treated with tamoxifen monotherapy. Mean duration of treatment was 13.3 months, mean follow-up 26.8 months. A total of 44 renal units were affected by hydronephrosis and covered by DJ stents. Radiological regression of fibrosis was detected in 22 cases (71.0%); removal of ureteral stents was possible in 27/44 renal units (61.4%) and 17/29 patients (58.6%), respectively. Most patients showed only mild or no side effects of therapy. In 7 cases (22.3%) tamoxifen therapy had to be abandoned because of severe side effects, progression of fibrosis or persistent intolerance. Conclusions: Tamoxifen is an alternative in the medical treatment of RPF, especially if patients want to avoid glucocorticoids. The potential of regression of fibrosis seems to be slightly inferior and the relapse rate is higher compared to steroids, but the rate of successful DJ removals is comparable. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article presents a study which investigates the association of peripapillary retinal nerve fibre layer (RFNL) thinning and macular ganglion cell layer (GCL) with white and grey matter brain volume in multiple sclerosis (MS) patients with and without an optic neuritis history. The study performed retinal examination with spectral domain optical coherence tomography. The result of the study shows that the GCL and RNFL were linked to whole brain as well as grey and white matter atrophy.

The article discusses research which investigate alterations of periventricular small blood vessel appearance in relation to T2 lesion count in patients with multiple sclerosis and clinically isolated syndrome using the 7 Tesla magnetic resonance imaging (MRI) technique. The study showed significantly decreased venous density in patients with multiple sclerosis patients. It revealed that alterations of venous density in multiple sclerosis in inversely associated with T2 lesion count.

Objective: To investigate the influence of CYP2D6 polymorphisms on outcomes and health-related quality of life of patients with retroperitoneal fibrosis (RPF) receiving tamoxifen (TMX). TMX is an effective alternative to corticosteroids for patients with RPF. Conversion of TMX to more potent endoxifen is dependent on enzyme activity of CYP2D6.Materials and Methods: CYP2D6 genotyping and phenotype prediction of all patients treated with TMX between 02/2007 and 01/2018 was assessed using multiplex polymerase chain reaction (PCR). Groups were classified by phenotype: extensive (EM) vs poor and intermediate (PM + IM) vs ultrarapid metabolizer (UM). Retrospective evaluation of outcome (including magnetic resonance imaging and positron emission tomography-computed tomography) and health-related quality of life using the SF-36 was performed.Results: A total of 63/194 patients received TMX, 40/63 with complete follow-up were sequenced: Twenty-nine patients with EM phenotype, 8 PM + IM and 3 UM. The median therapy duration was 364.5 days with a mean follow-up of 62.9 months. Seven therapy terminations occurred due to lack of response (17.5%), including all UM patients (P <.001). Magnetic resonance imagings showed a regression of fibrosis for EM and PM + IM in 69% and 62.5% of cases and a progression for UM in 100% (P = .004). In positron emission tomography-computed tomography, glucose utilization of RPF decreased significantly for EM and PM + IM. The physical sum-score of SF-36 improved for EM and PM + IM and decreased for UM (P <.05). The removal of DJ-stents was successful for EM, PM + IM, and UM in 48.3%, 75%, and 0% of cases (P = .0581).Conclusion: Contrary to expectations, UM showed the lowest success rate, which concludes that genotyping of RPF-patients may be useful in the sense of a tailored-therapy. [ABSTRACT FROM AUTHOR]