Frederik Bartels

All Publications

• Brain atrophy patterns in anti-IgLON5 disease. Brain : a journal of neurology Yogeshwar, S. M., Bartels, F., Grüter, T., Muñiz-Castrillo, S., Picard, G., Crijnen, Y. S., Bernard, E., Heidbreder, A., Zekeridou, A., Ringelstein, M., Kraft, A., Kovac, S., Wandinger, K. P., de Vries, J. M., Boon, A. J., Veenbergen, S., Geis, C., Penner, L., Melzer, N., Leypoldt, F., Blaabjerg, M., Pittock, S. J., Gaig, C., Sabater, L., Santamaria, J., Graus, F., Dalmau, J., Prüss, H., Höftberger, R., Schreiner, B., McKeon, A., Lewerenz, J., Irani, S., Mignot, E., Titulaer, M. J., Ayzenberg, I., Honnorat, J., Finke, C. 2025

  Abstract

  Anti-IgLON5 disease is an autoimmune encephalitis that presents with a heterogenous clinical phenotype, including sleep disorders, movement abnormalities and bulbar involvement. It is characterised by autoantibodies against IgLON5, 85% association with HLA-DQB1*05:∼ and a brainstem-dominant tauopathy. Cellular and murine models report pathogenic effects of the autoantibodies, and neurodegenerative factors suggest progressive atrophy as a common sequela. However, evidence from in vivo patient data and long-term follow up are limited. Further, the degree of progression remains elusive. In this multi-centre study, clinical and brain MRI data were collected from 127 patients across twelve countries to investigate the relationships between clinical presentations and the development of distinct brain atrophy patterns. Our data show that most patients develop a complex multi-system phenotype as the disease progresses, however, neuromuscular manifestations rarely emerge at later disease stages. By comparison to healthy controls, this disease presents with severe sub-structure specific atrophy, especially affecting the hypothalamus, brainstem, accumbens and basal ganglia which, in age-independent analyses, show significant ventricular enlargement and also suggest progression of brainstem atrophy over the disease course. Moreover, the focality of atrophy was functionally linked to specific symptoms, with more severe involvement of the basal ganglia in patients with movement disorders, and greater atrophy in the hippocampus and thalamus in patients with cognitive impairment. Taken together, our results provide evidence of distinct atrophy patterns in anti-IgLON5 disease, which closely mirror sites of pathophysiologic processes, including autoantibody binding and tau deposition. Our data emphasize the brainstem as the pathophysiological hub of the disease and provide normative data for the incorporation of atrophy measurements into routine clinical assessments and future treatment studies to monitor disease trajectory and evaluate future treatment strategies.

  View details for DOI 10.1093/brain/awaf256

  View details for PubMedID 40650880

• Distinguishing Transient From Persistent Brain Structural Changes in Pediatric Patients With Acute Disseminated Encephalomyelitis NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION Millward, J., Pilgrim, E., Baumann, M., Wendel, E., El Naggar, I., Bertolini, A., Bartels, F., Finke, C., Paul, F., Niendorf, T., Rostasy, K., Waiczies, S. 2025; 12 (1): e200337

  Abstract

  Pediatric patients with acute disseminated encephalomyelitis (ADEM) are at risk of impaired brain growth, with long-term neuropsychiatric consequences. We previously reported transient expansions of cerebral ventricle volume (VV) in experimental autoimmune encephalomyelitis, which subsequently normalized. In this study, we investigated changes in VV in ADEM in relation to other brain structures and clinical outcomes.We investigated brain MRI scans acquired in routine clinical practice from a multicenter cohort of 61 pediatric patients with ADEM, of whom 39 were myelin oligodendrocyte glycoprotein (MOG) antibody-positive. Patients were compared with 1,219 pediatric healthy controls (HCs). Volumes of multiple brain structures were computed using a contrast-agnostic machine learning-based tool and analyzed with mixed-effect models regarding other clinical parameters.Patients with ADEM had larger VV than HCs at initial clinical presentation, before immune therapy. Most of the patients showed further VV increases within 2 months after disease onset. Patients had smaller brain volumes than HCs, with specific reductions in deep gray matter structures. These changes were more pronounced in MOG antibody-negative patients.Of the patients with more than 2 MRI scans, 12 of 22 resolved their VV expansion back to within 15% of baseline values while 10 of 22 had persistently increased VV at the last available MRI within 1 year from onset. Patients with persistent VV expansion had greater reductions in volumes of other brain structures at the last MRI than patients whose VV resolved and were more likely to have residual neurologic signs. The VV resolving and nonresolving patients did not differ regarding age, sex, elevated CSF cell counts at baseline, or occurrence of relapses. However, patients with a larger magnitude of VV expansion-≥90% of baseline volume-were more likely to be in the nonresolving group.We could distinguish between 2 outcomes of VV changes in ADEM: one in which the VV expanded but ultimately returned to normal and one in which the expansions continued after disease onset and treatment but failed to resolve. The latter was associated with reduced brain volume, particularly in deep gray matter structures. This highlights the necessity for patients with ADEM to undergo regular MRI scans to assess whether developing VV expansions indicate a greater risk of permanent brain atrophy.

  View details for DOI 10.1212/NXI.0000000000200337

  View details for Web of Science ID 001383869300001

  View details for PubMedID 39715470

  View details for PubMedCentralID PMC11676258