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Neuro-inflammation
Research paper
Attack-related damage of thalamic nuclei in neuromyelitis optica spectrum disorders
  1. Athina Papadopoulou1,2,3,
  2. Frederike Cosima Oertel1,2,
  3. Laura Gaetano3,4,5,
  4. Joseph Kuchling1,2,
  5. Hanna Zimmermann1,2,
  6. Claudia Chien1,2,
  7. Nadja Siebert1,2,
  8. Susanna Asseyer1,2,
  9. Judith Bellmann-Strobl1,2,
  10. Klemens Ruprecht1,6,
  11. M. Mallar Chakravarty7,8,
  12. Michael Scheel1,9,
  13. Stefano Magon3,4,
  14. Jens Wuerfel4,
  15. Friedemann Paul1,2,6,
  16. Alexander Ulrich Brandt1,2,10
  1. 1 Neurocure Clinical Research Center, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of health, Berlin, Germany
  2. 2 Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
  3. 3 Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
  4. 4 Medical Image Analysis Center, Basel, Switzerland
  5. 5 F. Hoffmann-La Roche, Basel, Switzerland
  6. 6 Department of Neurology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
  7. 7 Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Québec, Canada
  8. 8 Department of Psychiatry and Biomedical engineering, McGill University, Montreal, Québec, Canada
  9. 9 Department of Neuroradiology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
  10. 10 Department of Neurology, University of California Irvine, Irvine, California, USA
  1. Correspondence to Dr Alexander Ulrich Brandt, NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin 10117, Germany; alexander.brandt{at}charite.de

Abstract

Objectives In neuromyelitis optica spectrum disorders (NMOSD) thalamic damage is controversial, but thalamic nuclei were never studied separately. We aimed at assessing volume loss of thalamic nuclei in NMOSD. We hypothesised that only specific nuclei are damaged, by attacks affecting structures from which they receive afferences: the lateral geniculate nucleus (LGN), due to optic neuritis (ON) and the ventral posterior nucleus (VPN), due to myelitis.

Methods Thirty-nine patients with aquaporin 4-IgG seropositive NMOSD (age: 50.1±14.1 years, 36 women, 25 with prior ON, 36 with prior myelitis) and 37 healthy controls (age: 47.8 ± 12.5 years, 32 women) were included in this cross-sectional study. Thalamic nuclei were assessed in magnetic resonance images, using a multi-atlas-based approach of automated segmentation. Retinal optical coherence tomography was also performed.

Results Patients with ON showed smaller LGN volumes (181.6±44.2 mm3) compared with controls (198.3±49.4 mm3; B=−16.97, p=0.004) and to patients without ON (206.1±50 mm3 ; B=−23.74, p=0.001). LGN volume was associated with number of ON episodes (Rho=−0.536, p<0.001), peripapillary retinal nerve fibre layer thickness (B=0.70, p<0.001) and visual function (B=−0.01, p=0.002). Although VPN was not smaller in patients with myelitis (674.3±67.5 mm3) than controls (679.7±68.33; B=−7.36, p=0.594), we found reduced volumes in five patients with combined myelitis and brainstem attacks (B=−76.18, p=0.017). Volumes of entire thalamus and other nuclei were not smaller in patients than controls.

Conclusion These findings suggest attack-related anterograde degeneration rather than diffuse thalamic damage in NMOSD. They also support a potential role of LGN volume as an imaging marker of structural brain damage in these patients.

  • thalamus
  • neurodegeneration
  • optic neuritis
  • lateral geniculate nucleus
  • transsynaptic degeneration

https://doi.org/10.1136/jnnp-2018-320249

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    Footnotes

    • Contributors Conception and design of the study: AP and AB. Acquisition, analysis and interpretation of data: AP, FCO, LG, JK, HZ, CC, NS, SA, JB-S, KR, MC, MS, SM, JW, FP and AB. Drafting the manuscript or figures: AP, FCO, JK, HZ, CC, NS, MC, SM, JW, FP and AB.

    • Funding This study was supported by the ‘Deutsche Forschungsgemeinschaft’ (grant DFG Exc. 257) and the German Federal Ministry for Education and Research (BMBF; grant N2-ADVISIMS: 16GW0079) to FP and AB and by the Swiss National Science Foundation (project number P300PB_174480) to AP.

    • Competing interests AP has received speaker-fee from Sanofi-Genzyme and travel support from Bayer AG, Teva and F. Hoffmann-La Roche. Her research was supported by the University of Basel, the Swiss Multiple Sclerosis Society and the ‘Stiftung zur Förderung der gastroenterologischen und allgemeinen klinischen Forschung sowie der medizinischen Bildauswertung’. The current research work was supported by the Swiss National Science Foundation (Project number: P300PB_174480). FCO was employee of Nocturne UG, not in context of this work. LG was a temporary employee of Novartis AG and is currently an employee of F. Hoffmann-La Roche; her contribution to this work was prior to her employment in F. Hoffmann-La Roche. JK received conference registration fees from Biogen and financial research support from Krankheitsbezogenes Kompetenznetzwerk Multiple Sklerose (KKNMS). HZ received research grants from Novartis and speaker fees from Teva. CC has nothing to disclose. NS has nothing to disclose. SA reports travel grants from Celgene, unrelated to this project. JB-S has received travel grants and speaking fees from Bayer Healthcare, Biogen Idec, Merck Serono, Sanofi-Aventis/Genzyme, Teva Pharmaceuticals, and Novartis. KR served on the scientific advisory board for Sanofi-Aventis/Genzyme, Novartis, and Roche; received travel funding and/or speaker honoraria from Bayer Healthcare, Biogen Idec, Merck Serono, Sanofi-Aventis/Genzyme, Teva Pharmaceuticals, Novartis, and Guthy Jackson Charitable Foundation; is an academic editor for PLoS ONE; receives publishing royalties from Elsevier; and received research support from Novartis and German Ministry of Education and Research. MC has nothing to disclose. MS has nothing to disclose. SM has received research support from Swiss MS Society, Swiss National Science Foundation, University of Basel and Stiftung zur Förderung der gastroenterologischen und allgemeinen klinischen Forschung sowie der medizinischen Bildauswertung. He also received travel support from Biogen and Genzyme. JW is CEO of MIAC AG Basel, Switzerland. He served on scientific advisory boards of Actelion, Biogen, Genzyme-Sanofi, Novartis, and Roche. He is or was supported by grants of the EU (Horizon2020), German Federal Ministeries of Education and Research (BMBF) and of Economic Affairs and Energy (BMWI). FP serves on the scientific advisory board for Novartis; received speaker honoraria and travel funding from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Merck Serono, Alexion, Chugai, MedImmune, and Shire; is an academic editor for PLoS ONE; is an associate editor for Neurology® Neuroimmunology and Neuroinflammation; consulted for SanofiGenzyme, Biogen Idec, MedImmune, Shire, and Alexion; and received research support from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Alexion, Merck Serono, German Research Council, Werth Stiftung of the City of Cologne, German Ministry of Education and Research, Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, Arthur Arnstein Founda-tion Berlin, Guthy Jackson Charitable Foundation, and National Multiple Sclerosis of the USA. AUB is cofounder and shareholder of technology startups Motognosis and Nocturne UG. He is named as inventor on several patent applications describing MS serum biomarkers, perceptive visual computing and retinal image analysis.

    • Patient consent for publication All participants gave written informed consent before inclusion in the study.

    • Ethics approval Ethikkommission der Charité—Universitätsmedizin Berlin (EA1/131/09).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Data are available upon reasonable request.

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