Search

Progressive multifocal leukoencephalopathy (PML) is a severe complication of natalizumab treatment. Restoring immune function by plasmapheresis/immunoadsorption (PLEX/IA) is important for the outcome of PML. We report on four multiple sclerosis (MS) patients whom developed PML during natalizumab treatment, in whom we measured serum natalizumab concentrations before and during PLEX. Depending on the serum natalizumab concentration at the time of PML diagnosis, the number of PLEX treatments necessary to reach subtherapeutic serum natalizumab concentrations is variable. Measuring serum natalizumab concentrations before and during PLEX is helpful to determine the optimum number of PLEX treatments in individual MS patients with PML. [ABSTRACT FROM AUTHOR]

The article presents a research which evaluates the association of vascular and neurodegenerative disease with Virchow-Robin spaces (VRS) in patients with multiple sclerosis (MS). Mentioned is the use of high-resolution 7 Tesla (T) magnetic resonance imaging (MRI) during the study. Noted are increased numbers of VRS in MS cases.

Objectives: To examine the feasibility and value of 7 T 3D T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) and Double Inversion Recovery (DIR) MR sequences for lesion detection in multiple sclerosis (MS).Methods: High-resolution 3D-FLAIR and 3D-DIR MR sequences at 7 T were obtained using magnetisation preparation (MP), and compared with 2D-T2-weighted and 3D-T1-weighted sequences in 10 MS patients and five healthy controls. We determined contrast ratios and counted lesions according to anatomical location.Results: MR imaging at 7 T was safe and allowed multi-contrast imaging within clinically acceptable imaging times. Lesion to white matter (WM) and grey matter (GM) contrast ratios were higher in 3D-MP-FLAIR and 3D-MP-DIR compared with 2D-T2 and 3D-T1. Cortical (mixed+intra-cortical) and total lesion counts were 97/592 on 3D-MP-FLAIR and 100/558 on 3D-MP-DIR compared with 84/384 on 2D-T2 and 42/442 on 3D-T1. More juxta-cortical lesions were seen with 3D-MP-FLAIR (205) and 3D-MP-DIR (133) than with 2D-T2 (125) and 3D-T1 (70). Finally, higher numbers of lesions were found for deep WM lesions: 176 for 3D-MP-FLAIR and 196 for 3D-MP-DIR vs. 155 for 2D-T2 and 131 for 3D-T1.Conclusions: Near isotropic 3D-MP-FLAIR and 3D-MP-DIR allows high quality T2-weighted MR imaging in MS at 7 T, improving (cortical) lesion detection. [ABSTRACT FROM AUTHOR]

Objective: To develop a visual rating scale for posterior atrophy (PA) assessment and to analyse whether this scale aids in the discrimination between Alzheimer's disease (AD) and other dementias.Methods: Magnetic resonance imaging of 118 memory clinic patients were analysed for PA (range 0-3), medial temporal lobe atrophy (MTA) (range 0-4) and global cortical atrophy (range 0-3) by different raters. Weighted-kappas were calculated for inter- and intra-rater agreement. Relationships between PA and MTA with the MMSE and age were estimated with linear-regression analysis.Results: Intra-rater agreement ranged between 0.93 and 0.95 and inter-rater agreement between 0.65 and 0.84. Mean PA scores were higher in AD compared to controls (1.6  ±  0.9 and 0.6  ±  0.7, p  <  0.01), and other dementias (0.8 ± 0.8, p  <  0.01). PA was not associated with age compared to MTA (B = 1.1 (0.8) versus B = 3.1 (0.7), p  <  0.01)). PA and MTA were independently negatively associated with the MMSE (B = -1.6 (0.5), p  <  0.01 versus B = -1.4 (0.5), p  <  0.01).Conclusion: This robust and reproducible scale for PA assessment conveys independent information in a clinical setting and may be useful in the discrimination of AD from other dementias. [ABSTRACT FROM AUTHOR]

Many technical developments keep occurring in the field of MRI that could benefit image acquisition in the field of diagnostic neuroradiology. While there is much focus on the potential advantages of 3T and higher field strengths, it is often unclear whether these are cosmetic only, or convey clinically relevant diagnostic value. The increased signal-to-noise at 3T is certainly beneficial in different ways particularly for the acquisition of isotropic 3D sequences like FLAIR. Single-slab 3D sequences can now be obtained with multiple contrasts in clinically attainable data acquisition times and could revolutionize MRI to evolve into a fundamentally multi-planar technique, rather similar to what has happened with the introduction of multi-detector row CT. [ABSTRACT FROM AUTHOR]

Driven by increasing numbers of newly identified genetic defects and new insights into the field of inherited muscle diseases, neuromuscular imaging in general and magnetic resonance imaging (MRI) in particular are increasingly being used to characterise the severity and pattern of muscle involvement. Although muscle biopsy is still the gold standard for the establishment of the definitive diagnosis, muscular imaging is an important diagnostic tool for the detection and quantification of dystrophic changes during the clinical workup of patients with hereditary muscle diseases. MRI is frequently used to describe muscle involvement patterns, which aids in narrowing of the differential diagnosis and distinguishing between dystrophic and non-dystrophic diseases. Recent work has demonstrated the usefulness of muscle imaging for the detection of specific congenital myopathies, mainly for the identification of the underlying genetic defect in core and centronuclear myopathies. Muscle imaging demonstrates characteristic patterns, which can be helpful for the differentiation of individual limb girdle muscular dystrophies. The aim of this review is to give a comprehensive overview of current methods and applications as well as future perspectives in the field of neuromuscular imaging in inherited muscle diseases. We also provide diagnostic algorithms that might guide us through the differential diagnosis in hereditary myopathies. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of a higher magnetic field strength of 3 Tesla (T) on the detection rate of cortical lesions in multiple sclerosis (MS) patients, in particular using a dedicated double inversion recovery (DIR) pulse sequence.Methods: Thirty-four patients with clinically isolated syndromes or definite MS were included. All patients underwent magnetic resonance imaging (MRI) at 1.5 T and 3 T, including T2-weighted turbo spin echo (TSE), fluid-attenuated inversion recovery (FLAIR) and DIR sequences. All images were analysed for focal lesions categorised according to their anatomical location.Results: The total number of detected lesions was higher at 3 T across all pulse sequences. We observed significantly higher numbers of lesions involving the cortex at 3 T using a DIR sequence. DIR at 3 T showed 192% more pure intracortical (p < 0.001) and 30% more mixed grey matter-white matter lesions (p = 0.008). No significant increase in cortical lesions could be detected on the FLAIR and T2-weighted images. Using the T2-weighted and FLAIR sequences, significantly more lesions could be detected at 3 T in the infratentorial, periventricular and juxtacortical white matter.Conclusion: DIR brain MR imaging at 3 T substantially improves the sensitivity of the detection of cortical lesions compared with the standard magnetic field strength of 1.5 T. [ABSTRACT FROM AUTHOR]

Unlabelled: High field MRI operating at 3 T is increasingly being used in the field of neuroradiology on the grounds that higher magnetic field strength should theoretically lead to a higher diagnostic accuracy in the diagnosis of several disease entities. This Editorial discusses the exhaustive review by Wardlaw and colleagues of research comparing 3 T MRI with 1.5 T MRI in the field of neuroradiology. Interestingly, the authors found no convincing evidence of improved image quality, diagnostic accuracy, or reduced total examination times using 3 T MRI instead of 1.5 T MRI. These findings are highly relevant since a new generation of high field MRI systems operating at 7 T has recently been introduced.Key Points: • Higher magnetic field strengths do not necessarily lead to a better diagnostic accuracy. • Disadvantages of high field MR systems have to be considered in clinical practice. • Higher field strengths are needed for functional imaging, spectroscopy, etc. • Disappointingly there are few direct comparisons of 1.5 and 3 T MRI. • Whether the next high field MR generation (7 T) will improve diagnostic accuracy has to be investigated. [ABSTRACT FROM AUTHOR]

Previous functional magnetic resonance imaging (fMRI) studies showed an abnormal brainstem-to-cortex functional connectivity (FC) in major depressive disorder. However, only few studies analyzed brainstem substructures in treatment-resistant depression (TRD). In this study, we analyzed resting-state seed-based FC between midbrain, pons, medulla oblongata and cortical/subcortical brain regions in patients with TRD (n = 24) and age- and sex-matched healthy controls (n = 24). FC was analyzed in each group and compared between groups. Correlation analyses assessed the relationship between FC strength and depressive symptom severity in regions showing significant group differences in seed-based connectivity. Our findings reveal an increased FC in the midbrain and pons to the precentral gyrus, postcentral gyrus, and temporal gyrus in patients with TRD compared to healthy controls. Interestingly, in TRD patients, FC between midbrain and cortex was negatively correlated with BDI-II scores, indicating a relationship between altered connectivity and self-reported depression severity. It is essential to note that our naturalistic, cross-sectional approach precludes causal conclusions regarding the relationship between FC and pathophysiology of TRD. The small sample size necessitates confirmation in a larger cohort. Midbrain/pons-to-cortex FC was increased in patients with TRD compared to healthy controls. Future studies should explore the relationship between abnormal brainstem-to-cortex FC and depressive symptomatology in more detail., Competing Interests: Declaration of competing interest RS took part in an educational event sponsored by Livanova. HF received speaker‘s honararia and served as advisor for Recordati Pharma GmbH and Janssen-Cilag Gmbh. AN received lecture fees from Novartis and Merck. TK received honoraria for talks and/or advisory board activities from Allergan, Janssen-Cilag, Idorsia, Lilly, Lundbeck, Otsuka, Neuraxpharm, Schwabe and Teva. HBM took part in educational events sponsored by Livanova and Rovi. AG, ZH, TF, TB, CS, NM, AB, MW, SB declare no conflict of interest., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Rationale and Objectives: Training Convolutional Neural Networks (CNN) requires large datasets with labeled data, which can be very labor-intensive to prepare. Radiology reports contain a lot of potentially useful information for such tasks. However, they are often unstructured and cannot be directly used for training. The recent progress in large language models (LLMs) might introduce a new useful tool in interpreting radiology reports. This study aims to explore the use of the LLM to classify radiology reports and generate labels. These labels will be utilized then to train a CNN to detect ankle fractures to evaluate the effectiveness of using automatically generated labels., Materials and Methods: We used the open-weight LLM Mixtral-8×7B-Instruct-v0.1 to classify radiology reports of ankle x-ray images. The generated labels were used to train a CNN to recognize ankle fractures. The model's accuracy, sensitivity, specificity, and area under the receiver operating characteristics curve were used for evaluation., Results: Using common prompt engineering techniques, a prompt was found that reached an accuracy of 92% on a test dataset. By parsing all radiology reports using the LLM, a training dataset of 15,896 images and labels was created. Using this dataset, a CNN was trained, which achieved an accuracy of 89.5% and an area under the receiver operating characteristic curve of 0.926 on a test dataset., Conclusion: Our classification model based on labels generated with a large language model achieved high accuracy. This performance is comparable to models trained with manually labeled data, demonstrating the potential of language models in automating the labeling process., Summary: Large language models can be used to reliably detect pathologies in radiology reports., Key Results: In this study, 7561 radiological reports of ankle X-ray images were automatically classified as describing an ankle fracture or not using a large language model. Using a dataset of 250 reports, the language model showed a classification accuracy of 92%. The generated labels were used to train an image classifier to detect ankle fractures on X-ray images. 15,896 images were used for training. The resulting model achieved an accuracy of 89.5% on a test dataset., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background High-quality translations of radiology reports are essential for optimal patient care. Because of limited availability of human translators with medical expertise, large language models (LLMs) are a promising solution, but their ability to translate radiology reports remains largely unexplored. Purpose To evaluate the accuracy and quality of various LLMs in translating radiology reports across high-resource languages (English, Italian, French, German, and Chinese) and low-resource languages (Swedish, Turkish, Russian, Greek, and Thai). Materials and Methods A dataset of 100 synthetic free-text radiology reports from CT and MRI scans was translated by 18 radiologists between January 14 and May 2, 2024, into nine target languages. Ten LLMs, including GPT-4 (OpenAI), Llama 3 (Meta), and Mixtral models (Mistral AI), were used for automated translation. Translation accuracy and quality were assessed with use of BiLingual Evaluation Understudy (BLEU) score, translation error rate (TER), and CHaRacter-level F-score (chrF++) metrics. Statistical significance was evaluated with use of paired t tests with Holm-Bonferroni corrections. Radiologists also conducted a qualitative evaluation of translations with use of a standardized questionnaire. Results GPT-4 demonstrated the best overall translation quality, particularly from English to German (BLEU score: 35.0 ± 16.3 [SD]; TER: 61.7 ± 21.2; chrF++: 70.6 ± 9.4), to Greek (BLEU: 32.6 ± 10.1; TER: 52.4 ± 10.6; chrF++: 62.8 ± 6.4), to Thai (BLEU: 53.2 ± 7.3; TER: 74.3 ± 5.2; chrF++: 48.4 ± 6.6), and to Turkish (BLEU: 35.5 ± 6.6; TER: 52.7 ± 7.4; chrF++: 70.7 ± 3.7). GPT-3.5 showed highest accuracy in translations from English to French, and Qwen1.5 excelled in English-to-Chinese translations, whereas Mixtral 8x22B performed best in Italian-to-English translations. The qualitative evaluation revealed that LLMs excelled in clarity, readability, and consistency with the original meaning but showed moderate medical terminology accuracy. Conclusion LLMs showed high accuracy and quality for translating radiology reports, although results varied by model and language pair. © RSNA, 2024 Supplemental material is available for this article.

Background: Diagnosing multiple sclerosis (MS) is challenging due to diverse symptoms and the absence of specific biomarkers. Concurrent autoimmune diseases (AID) or non-specific antibodies further complicate diagnosis, progression monitoring, and management. Data on AID prevalence in MS patients are sparse. This study aims to identify concurrent AIDs alongside MS., Methods: In this retrospective single-center study, we analyzed patient records at our university hospital from 2010 to 2017, focusing on cases suspected of inflammatory demyelinating disease. The 2017 McDonald criteria were applied. Additionally, we measured neurofilament light (NfL) levels from available CSF samples in our biobank., Results: We identified a total of 315 patients, of whom 66% were women. In total, 13.7% of all patients had concurrent AID, while 20.3% had isolated antibody findings without AID. The most common AID was autoimmune thyroiditis (8.9%), followed by chronic inflammatory skin diseases (1.6%), arthritis (1%), type 1 diabetes (1%), Sjögren's syndrome (0.6%), and inflammatory bowel diseases (0.6%). Cardiolipin antibodies were the most frequent isolated antibody finding (8.6%). Our data showed that, from the perspective of the initial demyelinating event, neither comorbid AID nor isolated antibodies significantly influenced relapses or MS progression over a median follow-up of 9 months. Standard CSF parameters and NfL levels were similar between the groups at the time of MS diagnosis., Conclusion: Our study shows that AIDs, particularly autoimmune thyroiditis, frequently occur at the onset of MS. The proportion of AIDs commonly treated with immunomodulatory therapy in our cohort was similar to that observed in the general population. Comorbid AID did not affect NfL levels, indicating similar disease activity. Future research should explore new AID emergence during the course of MS, especially considering the increased incidence of rheumatic diseases later in life., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the institutional ethics committee (no. 8172-BO-K-2018). Consent for publication Not applicable. Competing interests The authors declare no conflict of interest. Outside the submitted work, the authors received honoraria for lectures, travel grants, or research grants. KFJ received research support from Else Kröner Fresenius Foundation and travel compensation and congress fee from Merck and Novartis. TT received honoraria from Boehringer Ingelheim, Janssen and Galapagos. LML reports no disclosures. FFK received travel grants from Merck and Novartis. AH reports no disclosures. LH reports no disclosures. YEG reports no disclosures. PS reports no disclosures. KWS reports honoraria for lectures or travel reimbursements for attending meetings from Biogen, Merck, Bavarian Nordic and Bristol-Myers Squibb as well as research support from Bristol-Myers Squibb. JS received lecture fees from Merck and Sanofi, and travel grant from Novartis and Sanofi. MPW received speaker or consultancy honoraria from Alexion, Bayer Healthcare, Biogen, Biologix, Bristol Myers Squibb, Celgene, Genilac, Imcyse, IXICO, Icometrix, Medison, Merck-Serono, Novartis, Roche, Sanofi-Genzyme, and publication royalties from Springer and Elsevier. TW reports honoraria for lectures and travel grants from Abbvie, Biogen, Boehringer Ingelheim, Celgene, Chugai, CSL Behring, Euroimmun, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, Siemens, Takeda, UCB. CK received lecture and consultancy fees from Biogen, Roche, and Novartis. RP received honoraria for lecturing and consulting from Alexion, Bayer Healthcare, Biogen, Bristol-Mayers Squibb, Hexal, Merck Serono, Mylan, Novartis, Roche, Sanofi Genzyme. He received research funds from Merck Serono and Novartis. HT has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Alexion, Bayer, Biogen, Bristol-Myers Squibb, Celgene, Diamed, Fresenius, Fujirebio, GlaxoSmithKline, Horizon, Janssen-Cilag, Merck, Novartis, Roche, Sanofi-Genzyme, Siemens, and Teva. All not related to the present work. SG received consulting and/or speaker honoraria from Alexion, Alnylam Pharmaceuticals, AstraZeneca, GSK, Pfizer and Merck. His research is supported by the Deutsche Forschungsgemeinschaft (DFG), Else Kröner Fresenius Foundation, Hannover Biomedical Research School (HBRS), Alnylam Pharmaceuticals and CSL Behring. TS reports research support from Alnylam Pharmaceuticals, CSL Behring, Novartis, Siemens; honoraria for lectures and travel expenses for attending meetings from Alexion, Alnylam Pharmaceuticals, argenx, Bayer Vital, Biogen, Bristol Myers Squibb, Celgene, Centogene, CSL Behring, Euroimmun, Grifols, Hexal AG, Horizon, Janssen-Cilag, Merck Serono, Novartis, Pfizer, Roche, Sanofi, Siemens, Swedish Orphan Biovitrum, Teva, Viatris; consultant fees from Alexion, Alnylam Pharmaceuticals, Biogen, Centogene, CSL Behring, Grifols, Hexal AG, Janssen-Cilag, Merck Serono, Novartis, Roche, Sanofi, Swedish Orphan Biovitrum, Viatris., (© 2024. The Author(s).)

Background: We aimed to investigate the clinical, imaging and fluid biomarker characteristics in patients with antidiacylglycerol lipase alpha (DAGLA)-autoantibody-associated cerebellitis., Methods: Serum and cerebrospinal fliud (CSF) samples from four index patients were subjected to comprehensive autoantibody screening by indirect immunofluorescence assay (IIFA). Immunoprecipitation, mass spectrometry and recombinant protein assays were used to identify the autoantigen. Sera from 101 patients with various neurological symptoms and a similar tissue staining pattern as the index patient samples, and 102 healthy donors were analysed in recombinant cell-based IIFA (RC-IIFA) with the identified protein. Epitope characterisation of all positive samples was performed via ELISA, immunoblot, immunoprecipitation and RC-IIFA using different DAGLA fragments., Results: All index patients were relatively young (age: 18-34) and suffered from pronounced gait ataxia, dysarthria and visual impairments. Paraclinical hallmarks in early-stage disease were inflammatory CSF changes and cerebellar cortex hyperintensity in MRI. Severe cerebellar atrophy developed in three of four patients within 6 months. All patient samples showed the same unclassified IgG reactivity with the cerebellar molecular layer. DAGLA was identified as the target antigen and confirmed by competitive inhibition experiments and DAGLA-specific RC-IIFA. In RC-IIFA, serum reactivity against DAGLA was also found in 17/101 disease controls, including patients with different clinical phenotypes than the one of the index patients, and in 1/102 healthy donors. Epitope characterisation revealed that 17/18 anti-DAGLA-positive control sera reacted with a C-terminal intracellular DAGLA 583-1042 fragment, while the CSF samples of the index patients targeted a conformational epitope between amino acid 1 and 157., Conclusions: We propose that anti-DAGLA autoantibodies detected in CSF, with a characteristic tissue IIFA pattern, represent novel biomarkers for rapidly progressive cerebellitis., Competing Interests: Competing interests: RM, MS, NR, CR, LS, SH, YD, CP and LK are employees of EUROIMMUN, a company that manufactures diagnostic tests and instruments. RM, MS, SH, YD, CP, FB and LK have patent applications, concerning the detection of an autoantibody against DAGLA issued and pending. KB, IS, MC, MJ-L, FR, GL, DR, TS, MPW, KG, MO, CIB, SN, K-PW, VvP, BT and K-WS report no competing interests to the work described., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Progressive multifocal leukoencephalopathy (PML) is a life-threatening viral infection with no approved antiviral treatment., Objective: To determine whether restoring the compromised immune system of patients with PML with directly isolated allogeneic virus-specific (DIAVIS) T cells is a promising therapeutic strategy, especially if other curative options are absent., Design, Setting, and Participants: A retrospective case series of patients with PML who were treated with DIAVIS T cells was conducted between March 2020 and February 2022. T cells were isolated from healthy donors within 24 hours and targeted against the BK polyomavirus. Patients with PML were treated monocentrically. Eligibility for treatment with DIAVIS T cells was assessed for patients with confirmed PML, and exclusion criteria included stable PML disease and previous treatment with natalizumab., Exposure: Fresh DIAVIS T cells were administered with a maximum dose of 2 × 104 CD3+ cells/kg body weight. Remaining T cells were cryopreserved in divided doses and administered in additional treatments approximately 2 and 6 weeks later., Main Outcomes and Measures: Primary outcome measures were clinical response and survival of patients, compared with the outcomes of a historical reference group of PML cases receiving best supportive treatment (BST) and with recently published real-world data of patients with PML who were treated with immune checkpoint inhibition., Results: The study cohort consisted of 28 patients (median [IQR] age, 60 [51-72] years; 20 male [71.4%]). Twenty-two patients (79%) treated with DIAVIS T cells showed response, resulting in significant clinical stabilization or improvement and a reduction in viral load. Six individuals (21%) were classified as nonresponders, deteriorated rapidly, and died, as did 2 other patients during a 12-month follow-up. Older age was the only predictor of a poor treatment response. Survival analysis revealed better 12-month survival rates (hazard ratio, 0.42; 95% CI, 0.24-0.73; P =.02) from diagnosis for patients treated with DIAVIS T cells (18 of 26 [69%]; 12-mo survival rate, 69%) compared with historical controls with BST (57 of 113 [50%]; 12-mo survival rate, including censored data, 45%)., Conclusion and Relevance: This case series of DIAVIS T-cell therapy in PML provides first class IV evidence suggesting efficacy to reduce mortality and improve functional outcome. Further prospective studies are required to confirm these results.

The differential diagnosis of multiple sclerosis can present specific challenges in patients from Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific. In these areas, environmental factors, genetic background, and access to medical care can differ substantially from those in North America and western Europe, where multiple sclerosis is most common. Furthermore, multiple sclerosis diagnostic criteria have been developed primarily using data from North America and western Europe. Although some diagnoses mistaken for multiple sclerosis are common regardless of location, a comprehensive approach to the differential diagnosis of multiple sclerosis in Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific regions requires special consideration of diseases that are prevalent in those locations. A collaborative effort has therefore assessed global differences in multiple sclerosis differential diagnoses and proposed recommendations for evaluating patients with suspected multiple sclerosis in regions beyond North America and western Europe., Competing Interests: Declaration of interests JC declares receiving grants or research contracts from Biogen and Merck; personal compensation for consulting from Merck; payment or honoraria for lectures from Biogen, Merck, Bristol Myers Squibb, Novartis, and Roche; and support for attending meetings and travel from Merck. JC is a deputy chair International Medical and Scientific Board of Multiple sclerosis International Federation (MSIF), unpaid; and has received equipment, materials, drugs, medical writing, gifts, or other services from Novartis (Investigator initiated award). AJS declares receiving grant funding from National Institute of Neurological Disorders and Stroke, National Institutes of Health and Bristol Myers Squibb (investigator initiated award); has done contracted research with Sanofi, Biogen, Novartis, Actelion, and Genentech; has received personal compensation for consulting from Emmanuel Merck, Darmstadt, Serono and Octave Bioscience; has received payments or honoraria for lectures from Emmanuel Merck, Darmstadt, Serono; has received expert testimony from The Jacob D Fuchsberg Law Firm and Koskoff Koskoff & Bieder; is a participant on a Data Safety Monitoring Board for the Patient Centered Research Institute, and Yale University; declares participation on an advisory board for Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, TG Therapeutics, and Horizon Therapeutics; and is a content Chair for the American Academy of Neurology (AAN) Institute Multiple Sclerosis Quality Measure Development Work Group and Section Editor for Multiple Sclerosis and Related Disorders. JAC declares personal compensation for consulting from Astoria, Bristol-Myers Squibb, Convelo, EMD Serono, FiND Therapeutics, INMune, and Sandoz; and serving as an editor of Multiple Sclerosis Journal. BLB is funded by the National Multiple Sclerosis Society, and National Institute of Health; is a consultant for Roche, and Sanofi; and is a Board Director AAN (unpaid). TG has served as a consultant and received compensation from Genentech, Horizon, Sanofi, Alexion, and Greenwich Biosciences. BH declares grants from the European Union, Bundesministerium für Bildung und Forschung, and Deutsche Forschungsgemeinschaft; received personal compensation for consulting from Sandoz, Novartis, and GLG consulting; holds patents for antibodies against KIR4·1 in a subpopulation of patients with multiple sclerosis (2012) and genetic determinants of neutralising antibodies to interferon (filed 2010); and participated in a Data Safety and Monitoring Board for Novartis, Allergy Care DSMB, TG Therapeutics, and Polpharma, and Advisory Board for Novartis. HJK declares a research grant from the National Research Foundation of Korea and research support from Aprilbio, UCB, and Eisai; has received consultancy fees from Altos Biologics, AstraZeneca, Biogen, Daewoong, Kaigene, Kolon Life Science, MDimune, Merck Serono, and Roche; declares honoraria for lectures from Alexion, Eisai, GCPharma, Handok, Mitsubishi Tanabe Pharma, and Sanofi Genzyme; has received personal compensation for participation on a Data Safety Monitoring Board from Sanofi-Genzyme; has received compensation as Co-editor for the Multiple Sclerosis Journal and Associate Editor for the Journal of Clinical Neurology; and is a Vice President of Pan-Asian Committee on Treatment and Research in Multiple Sclerosis (unpaid). RAM declares grants or contracts from Biogen, Idec, and Roche. FM has received research funding to her institution from Sumaira Foundation, Genentech, Biogen, Horizon Therapeutics, US National Histitute Institute of Health, US Department of State, Foundation Pierre Fabre, and Novartis; has received consulting fees from Alexion, EMD Serono, Genentech, TG Therapeutics, and Horizon Therapeutics; and declares shares of the startup company Brain Capture (not related to the content of this manuscript). SDN declares grants or contracts (paid directly to institution) from Biogen, Roche, Genentech, National MS Society, Department of Defense, and Patient Centered Outcomes Research Institute; has received personal compensation for consulting from Biogen, Roche, Genentech, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, Novartis, Horizon Therapeutics, and TG Therapeutics; and is a study lead principal investigator for a Roche clinical trial programme. MAS declares personal honoraria for lectures from Roche, Biogen, Cinnagen, NanoAlvand, Merck, Novartis, and Abidi. DKS declares grants or research contracts from CNPq / Brazil 425331/2016–4 and 308636/2019–8, and Brazilian National Council for Scientific and Technological Development; has received investigator initiated awards from TEVA, Merck, and Biogen; has received personal compensation for consulting from Roche, and Alexion; declares personal honoraria for lectures from Roche, Alexion, Horizon, Merck, Americas Health Foundation; and is a member of International Society of Neuroimmunology, International Advisory Board (unpaid), and Academia Brasileira de Neurologia, Educational Committee (unpaid). DS declares a pilot research grant from the National MS Society paid to the Institution; declares receipt of personal honoraria for lecturing from Roche Pharmaceuticals; declares travel support from Roche Pharmaceutical; and is a Committee member and chair of Multiple Sclerosis International Federation (unpaid). AS has received grants or contracts from the Turkish MS Society, Istanbul University-Cerrahpasa Research Support Funds, and The Scientific and Technological Research Council of Türkiye Health Sciences Research Grants; has received consulting fees from Roche, Merck-Serono, Biogen Idec/Gen Pharma of Turkey , Sanofi-Genzyme, Novartis, and Alexion; has received honoraria for lectures from Sanofi-Genzyme, Novartis, TEVA, and Roche; and has received support for attending meetings from Sanofi-Genzyme, Roche, Merck-Serono, and Alexion. KT declares personal consulting fees from Merck and Eisai; declares payment for lectures from Merck, Eisai, Roche, and Terumo Blood and Cell Technology; and is a member of the Organizing Committee Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (unpaid). MW has received publication royalties from Springer and Elsevier; has received consultancy honoraria from Icometrix, Imcyse, Novartis, Sanofi, Merck, and Biologix; declares personal compensation for lectures or presentations from Alexion, Bayer Healthcare, Biogen, Biologix, Bristol Myers Squibb, Celgene, Genilac, Imcyse, Icometrix, Merck-Serono, Novartis, Roche, and Sanofi-Genzyme; and declares support for attending meetings from Merck-Serono. BGW declares royalties from RSR, Hospices Civils de Lyon, MVZ Labor PD Dr Volkmann und Kollegen GbR , and Oxford University; declares personal consulting fees from Roche, Horizon Therapeutics, Cambridge Pharmaceuticals, and Mitsubishi Tanabe; has received payments for lecture presentations from Roche and Horizon; has a patent planned for NMO-IgG for diagnosis of neuromyelitis optica; and declares participation on a Data Safety Monitoring Board and Advisory borads for Alexion MedImmune/VielaBio/Horizon, and UCB Biosciences. KF declares grants from Ministry of Education, Culture, Sports, Science and Technology of Japan and Ministry of Health, Welfare and Labor of Japan; has received personal compensation for consulting from Merck Biopharma, Japan Tobacco, and Abbvie; has received payment or honoraria forlectures and presentations from Biogen, Eisai, Mitsubishi Tanabe, Novartis, Chugai/Roche, Alexion, VielaBio/Horizon Therapeutics, Teijin, Asahi Kasei Medical, Merck, and Takeda; declares participation in an Advisory Board for Biogen, Mitsubishi Tanabe, Novartis, Chugai/Roche, Alexion, VielaBio/Horizon Therapeutics, and UCB; serves as President of the Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (unpaid), President of the Japanese Society of Neuroimmunology (unpaid), is a Board Member of the Japan Multiple Sclerosis Society (unpaid), is a board member of theEuropean Charcot Foundation (unpaid), and is a Member of the International Medical and Scientific Board, MSIF (unpaid). All other authors declared no competing interest., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Diagnostic criteria for progressive supranuclear palsy (PSP) include midbrain atrophy in MRI and hypometabolism in [ 18 F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) as supportive features. Due to limited data regarding their relative and sequential value, there is no recommendation for an algorithm to combine both modalities to increase diagnostic accuracy. This study evaluated the added value of sequential imaging using state-of-the-art methods to analyse the images regarding PSP features., Methods: The retrospective study included 41 PSP patients, 21 with Richardson's syndrome (PSP-RS), 20 with variant PSP phenotypes (vPSP) and 46 sex- and age-matched healthy controls. A pretrained support vector machine (SVM) for the classification of atrophy profiles from automatic MRI volumetry was used to analyse T1w-MRI (output: MRI-SVM-PSP score). Covariance pattern analysis was applied to compute the expression of a predefined PSP-related pattern in FDG-PET (output: PET-PSPRP expression score)., Results: The area under the receiver operating characteristic curve for the detection of PSP did not differ between MRI-SVM-PSP and PET-PSPRP expression score (p≥0.63): about 0.90, 0.95 and 0.85 for detection of all PSP, PSP-RS and vPSP. The MRI-SVM-PSP score achieved about 13% higher specificity and about 15% lower sensitivity than the PET-PSPRP expression score. Decision tree models selected the MRI-SVM-PSP score for the first branching and the PET-PSPRP expression score for a second split of the subgroup with normal MRI-SVM-PSP score, both in the whole sample and when restricted to PSP-RS or vPSP., Conclusions: FDG-PET provides added value for PSP-suspected patients with normal/inconclusive T1w-MRI, regardless of PSP phenotype and the methods to analyse the images for PSP-typical features., Competing Interests: Competing interests: H-JH has used atlas-based volumetric MRI analysis in industry-sponsored research projects. CB received a grant from the Hilde-Ulrichs-Stiftung, served as a consultant for Bial, Hormosan Pharma, Merz Pharmaceuticals and Zambon and received honoraria for scientific presentations from Abbvie, Bial, Stada Pharma, TAD Pharma, UCB Pharma and Zambon. MP-N received lecture fees from Abbott, Abbvie, Boston Scientific and served as consultant for Medtronic, Boston Scientific, Abbott, Zambon and Abbvie. SK was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy–ID 390857198), the Ehrmann Foundation and the Lüneburg Heritage. SK receives research funding from CurePSP and reports travel support from Life Molecular Imaging outside the submitted work. MK received honoraria for scientific presentations from Abbvie and Ever Pharma. JL reports speaker fees from Bayer Vital, Biogen, EISAI, TEVA and Roche, consulting fees from Axon Neuroscience and Biogen, author fees from Thieme medical publishers and W. Kohlhammer medical publishers and is inventor in a patent 'Oral Phenylbutyrate for Treatment of Human 4-Repeat Tauopathies' (EP 23 156 122.6) filed by LMU Munich. In addition, he reports compensation for serving as chief medical officer for MODAG, is beneficiary of the phantom share program of MODAG and is inventor in a patent 'Pharmaceutical Composition and Methods of Use' (EP 22 159 408.8) filed by MODAG, all activities outside the submitted work. J-JR received speaker honoraria from GE Healthcare. OS received research support from Life Molecular Imaging. HB received reader honoraria from Life Molecular Imaging and speaker honoraria from Novartis/AAA. MPW received speaker or consultancy honoraria from Alexion, Bayer Healthcare, Biogen, Biologix, Bristol Myers Squibb, Celgene, Genilac, Imcyse, IXICO, Icometrix, Medison, Merck-Serono, Novartis, Roche, Sanofi-Genzyme. Publication royalties from Springer and Elsevier. GH was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy–ID 390857198) and within the Hannover Cluster RESIST (EXC 2155–project number 39087428), the EU/EFPIA/Innovative Medicines Initiative (2) Joint Undertaking (IMPRIND grant no 116060), the European Joint Programme on Rare Diseases (Improve-PSP), Deutsche Forschungsgemeinschaft (DFG, HO2402/6-2 Heisenberg Program, HO2402/18-1 MSAomics), the VolkswagenStiftung (Niedersächsisches Vorab), the Petermax-Müller Foundation (Etiology and Therapy of Synucleinopathies and Tauopathies); participated in indurtry-sponsored research projects from Abbvie, Biogen, Biohaven, Novartis, Roche, Sanofi, UCB; served as a consultant for Abbvie, Alzprotect, Aprineua, Asceneuron, Bial, Biogen, Biohaven, Kyowa Kirin, Lundbeck, Novartis, Retrotope, Roche, Sanofi, UCB; received honoraria for scientific presentations from Abbvie, Bayer Vital, Bial, Biogen, Bristol Myers Squibb, Kyowa Kirin, Roche, Teva, UCB, Zambon; received publication royalties from Academic Press, Kohlhammer and Thieme. All other authors declare that they have no potential conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Magnetic resonance imaging is the most sensitive method for detecting inflammatory activity in multiple sclerosis, particularly in the brain where it reveals subclinical inflammation. Established MRI markers include contrast-enhancing lesions and active T2 lesions. Recent promising markers like slowly expanding lesions and phase rim lesions are being explored for monitoring chronic inflammation, but require further validation for clinical use. Volumetric and quantitative MRI techniques are currently limited to clinical trials and are not yet recommended for routine clinical use. Additionally, MRI is crucial for detecting complications from disease-modifying treatments and for implementing MRI-based pharmacovigilance strategies, such as in patients treated with natalizumab., Competing Interests: Disclosure N. Mahmoudi has nothing to disclose. M.P. Wattjes received speaker or consultancy honoraria from Alexion, Bayer Healthcare, Biogen, Biologix, Celgene, Genilac, Imcyse, IXICO, Icometrix, Medison, Merck-Serono, Novartis, Roche, Sanofi-Genzyme, Springer Healthcare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rationale and Objectives: First, to test the feasibility of cerebral blood flow (CBF) estimation using the pulse wave amplitude in flow-related enhancement (FREE) brain MRI in comparison to pseudo-continuous arterial spin labeling (pCASL-MRI). Second, the potential for acceleration was evaluated retrospectively., Materials and Methods: 24 healthy study participants between 20 and 61 years had cerebral MRI. Perfusion imaging was performed with a balanced steady-state free precession sequence for FREE-MRI and with pCASL-MRI for comparison., Results: The value distribution of the estimated CBF showed a high overlap in the histogram between 0 and 20 mL/100 g/min. However, disparity of the values occurred with more values between 20 and 60 mL/100 g/min using pCASL-MRI and more high values > 60 mL/100 g/min applying FREE-MRI. A Kolmogorov-Smirnov test confirmed a differing probability distribution (P = 0.62). The approximated CBF from FREE-MRI remained stable until only 50% of the acquired data was used. Values from using 40% of the data increased significantly compared to 90% or more (P ≤ 0.05). Values within the white matter presented no significant change after data reduction. The global and voxel-wise correlation coefficients towards pCASL-MRI presented stability during data reduction of FREE-MRI., Conclusion: In conclusion, the proposed technique allows a rough approximation of the CBF compared to pCASL-MRI. Further sequence optimization must be achieved to improve the measurement of relatively lowly perfused tissues. Nevertheless, it offers large potential for imaging speed optimization and enables perfusion-weighted images similarly to the color Doppler mode in ultrasound., Competing Interests: Declaration of Competing Interest The authors report no financial interests or potential conflicts of interest and have nothing to disclose., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Opportunistic viral infections in individuals with severe immunodeficiency can lead to fatal conditions such as progressive multifocal leukoencephalopathy (PML), for which treatment options are limited. These infections pose significant risks, especially when co-infections with other viruses occur. We describe a combined therapy approach using directly isolated allogeneic Human Polyomavirus 1 (also known as BKV) and Epstein-Barr virus (EBV) specific cytotoxic T-cells for the treatment of PML in conjunction with identified EBV in the cerebrospinal fluid (CSF) of a male patient infected with human immunodeficiency virus (HIV). A 53-year-old HIV-positive male, recently diagnosed with PML, presented with rapidly worsening symptoms, including ataxia, tetraparesis, dysarthria, and dysphagia, leading to respiratory failure. The patient developed PML even after commencing highly active antiretroviral therapy (HAART) 3 months prior. Brain magnetic resonance imaging (MRI) revealed multifocal demyelination lesions involving the posterior fossa and right thalamus suggestive of PML. In addition to the detection of human polyomavirus 2 (also known as JCV), analysis of CSF showed positive results for EBV deoxyribonucleic acid (DNA). His neurological condition markedly deteriorated over the following 2 months. Based on MRI, there was no evidence of Immune Reconstitution Inflammatory Syndrome contributing to this decline. The patient did not have endogenous virus-specific T-cells. We initiated an allogeneic, partially human leukocyte antigen-matched transfer of EBV and utilizing the cross-reactivity between BKV and JCV-BKV specific T-cells. This intervention led to notable neurological improvement and partial resolution of the MRI lesions within 6 weeks. Our case of a patient with acquired immune deficiency syndrome demonstrates that PML and concurrent EBV co-infection can still occur despite undergoing HAART treatment. This innovative experimental therapy, involving a combination of virus-specific T-cells, was demonstrated to be an effective treatment option in this patient., (© The Author(s), 2024.)

Competing Interests: JK received research grants for the multicentre investigator-initiated trials DOT-MS (NCT04260711, ZonMW) and BLOOMS (NCT05296161, ZonMW and Treatmeds); received consulting fees from F Hoffmann-La Roche, Biogen, Teva, Merck, Novartis, and Sanofi/Genzyme (all payments to institution); reports speaker relationships with F Hoffmann-La Roche, Biogen, Immunic, Teva, Merck, Novartis, and Sanofi/Genzyme (all payments to institution); and is on the adjudication committee of an MS clinical trial of Immunic (payments to institution only). MPW received speaker or consultancy honoraria from Alexion, Bayer Healthcare, Biogen, Biologix, Bristol Myers Squibb, Celgene, Genilac, Imcyse, IXICO, Icometrix, Medison, Merck-Serono, Novartis, Roche, and Sanofi/Genzyme; and has received publication royalties from Springer and Elsevier.

Optic neuritis is often an initial symptom in multiple sclerosis (MS) or clinically isolated syndrome (CIS), yet comprehensive studies using the 2017 McDonald criteria for MS are scarce. Patient records from our academic centre (2010-2018) were reviewed. Using the 2017 McDonald criteria, three groups were formed: MS optic neuritis (optic neuritis with confirmed MS), CIS optic neuritis (optic neuritis without confirmed MS) and suspected optic neuritis (sON). We compared clinical and paraclinical findings among the groups to identify predictors for CIS- or MS-optic neuritis. The study included 129 MS, 108 CIS, and 44 sON cases. The combination of visual impairment, dyschromatopsia, and retrobulbar pain was observed in 47% of MS patients, 42% of CIS patients, and 30% of sON patients. Dyschromatopsia was the strongest indicator of MS or CIS diagnosis in the backward regression model. 56% of MS patients had relative afferent pupillary defect, 61% optic nerve anomalies within magnetic resonance imaging, and 81% abnormal visual evoked potentials. Our results emphasize the challenges in diagnosing optic neuritis, as not all patients with objectively diagnosed MS exhibit the triad of typical symptoms. To address potentially missing clinical features, incorporating additional paraclinical findings is proposed., (© 2024. The Author(s).)

Magnetic resonance imaging (MRI) is the most sensitive technique for detecting inflammatory demyelinating lesions in multiple sclerosis (MS) and plays a crucial role in diagnosis and monitoring treatment effectiveness, and for predicting the disease course. In clinical practice, detection of MS lesions is mainly based on T2-weighted and contrast-enhanced T1-weighted sequences. Contrast-enhancing lesions (CEL) on T1-weighted sequences are related to (sub)acute inflammation, while new or enlarging T2 lesions reflect the permanent footprint from a previous acute inflammatory demyelinating event. These two types of MRI features provide redundant information, at least in regular monitoring of the disease. Due to the concern of gadolinium deposition after repetitive injections of gadolinium-based contrast agents (GBCAs), scientific organizations and regulatory agencies in Europe and North America have proposed that these contrast agents should be administered only if clinically necessary. In this article, we provide data on the mode of action of GBCAs in MS, the indications of the use of these agents in clinical practice, their value in MS for diagnostic, prognostic, and monitoring purposes, and their use in specific populations (children, pregnant women, and breast-feeders). We discuss imaging strategies that achieve the highest sensitivity for detecting CELs in compliance with the safety regulations established by different regulatory agencies. Finally, we will briefly discuss some alternatives to the use of GBCA for detecting blood-brain barrier disruption in MS lesions. CLINICAL RELEVANCE STATEMENT: Although use of GBCA at diagnostic workup of suspected MS is highly valuable for diagnostic and prognostic purposes, their use in routine monitoring is not mandatory and must be reduced, as detection of disease activity can be based on the identification of new or enlarging lesions on T2-weighted images. KEY POINTS: • Both the EMA and the FDA state that the use of GBCA in medicine should be restricted to clinical scenarios in which the additional information offered by the contrast agent is required. • The use of GBCA is generally recommended in the diagnostic workup in subjects with suspected MS and is generally not necessary for routine monitoring in clinical practice. • Alternative MRI-based approaches for detecting acute focal inflammatory MS lesions are not yet ready to be used in clinical practice., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)