Longitudinal optic neuritis-unrelated visual evoked potential changes in NMO spectrum disorders

Marius Ringelstein; Jens Harmel; Hanna Zimmermann; Alexander U Brandt; Friedemann Paul; Axel Haarmann; Mathias Buttmann; Martin W Hümmert; Corinna Trebst; Christoph Schroeder; Ilya Ayzenberg; Ingo Kleiter; Kerstin Hellwig; Joachim Havla; Tania Kümpfel; Sven Jarius; Brigitte Wildemann; Paulus Rommer; Martin S Weber; Hannah Pellkofer; Luise Röpke; Christian Geis; Nele Retzlaff; Uwe Zettl; Michael Deppe; Luisa Klotz; Kim Young; Jan-Patrick Stellmann; Matthias Kaste; Pawel Kermer; Wael Marouf; Florian Lauda; Hayrettin Tumani; Jonas Graf; Alexander Klistorner; Hans-Peter Hartung; Orhan Aktas; Philipp Albrecht; Neuromyelitis Optica Study Group (NEMOS)

doi:10.1212/WNL.0000000000008684

Longitudinal optic neuritis-unrelated visual evoked potential changes in NMO spectrum disorders

Neurology. 2020 Jan 28;94(4):e407-e418. doi: 10.1212/WNL.0000000000008684. Epub 2019 Dec 3.

Authors

Marius Ringelstein¹, Jens Harmel¹, Hanna Zimmermann¹, Alexander U Brandt¹, Friedemann Paul¹, Axel Haarmann¹, Mathias Buttmann¹, Martin W Hümmert¹, Corinna Trebst¹, Christoph Schroeder¹, Ilya Ayzenberg¹, Ingo Kleiter¹, Kerstin Hellwig¹, Joachim Havla¹, Tania Kümpfel¹, Sven Jarius¹, Brigitte Wildemann¹, Paulus Rommer¹, Martin S Weber¹, Hannah Pellkofer¹, Luise Röpke¹, Christian Geis¹, Nele Retzlaff¹, Uwe Zettl¹, Michael Deppe¹, Luisa Klotz¹, Kim Young¹, Jan-Patrick Stellmann¹, Matthias Kaste¹, Pawel Kermer¹, Wael Marouf¹, Florian Lauda¹, Hayrettin Tumani¹, Jonas Graf¹, Alexander Klistorner¹, Hans-Peter Hartung¹, Orhan Aktas¹, Philipp Albrecht²; Neuromyelitis Optica Study Group (NEMOS)

Collaborators

Neuromyelitis Optica Study Group (NEMOS):
Klemens Angstwurm, Antonios Bayas, Achim Berthele, Judith BellmannStrobl, Felix Bischof, Stefan Bittner, Tobias Böttcher, Johannes Brettschneider, Marcus DSouza, Barbara Ettrich, Jürgen Faiss, Benedikt Frank, Anna Gahlen, Achim Gass, Matthias Grothe, Kerstin Guthke, Eva Marie Habedank, Bernhard Hemmer, Frank Hoffmann, Olaf Hoffmann, Ulrich Hofstadt-van Oy, Jutta Junghans, Barbara Kaulen, Peter Kern, Christoph Kleinschnitz, Wolfgang Köhler, Melanie Korsen, Markus Kowarik, Markus Krumbholz, Stefan Langel, Martin Liebetrau, Ralf Linker, De-Hyung Lee, Felix Luessi, Martin Marziniak, Christoph Mayer, Stefanie Meister, Arthur Melms, Imke Metz, Christoph Münch, Oliver Neuhaus, Sabine Niehaus, Florence Pache, Marc Pawlitzki, Hans-Ulrich Puhlmann, Refik Pul, Kevin Rostásy, Lioba Rückriem, Klemens Ruprecht, Christoph Ruschil, Sven Schippling, Simon Schuster, Matthias Schwab, Makbule Senel, Jörn Peter Sieb, Nadja Siebert, Claudia Sommer, Annette Spreer, Martin Stangel, Andrea Steinbrecher, Heike Stephanik, Muriel Stoppe, Marie Süße, Björn Tackenberg, Florian Then-Bergh, Johannes Tünnerhoff, Christian Veauthier, Annette Walter, Klaus-Peter Wandinger, Clemens Warnke, Martin Weber, Robert Weissert, Heinz Wiendl, Christian Wilke, Alexander Winkelmann, Yavor Yalachkov, Lena Zeltner, Christian Zentner, Ulf Ziemann, Frauke Zipp

Affiliations

¹ From the Department of Neurology, Medical Faculty (M.R., J. Harmel, J.G., H.-P.H., O.A., P.A.), and Department of Neurology, Center for Neurology and Neuropsychiatry, LVR-Klinikum (M.R.), Heinrich Heine University Düsseldorf; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (H.Z., A.U.B., F.P.), Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, and Max Delbrueck Center for Molecular Medicine, Germany; Department of Neurology (A.U.B.), University of California Irvine; Department of Neurology (A.H., M.B.), University of Würzburg; Department of Neurology (M.B.), Caritas Hospital, Bad Mergentheim; Clinical Neuroimmunology and Neurochemistry (M.W.H.), Department of Neurology (C.T.), Hannover Medical School; Department of Neurology (C.S., I.A., I.K., K.H.), St. Josef Hospital, Ruhr University Bochum, Germany; Department of Neurology (I.A.), Sechenov First Moscow State Medical University, Moscow, Russia; Marianne-Strauß-Klinik (I.K.), Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke, Berg; Institute of Clinical Neuroimmunology (J. Halva, T.K., H.P.), University Hospital, Ludwig-Maximilians University, Munich; Molecular Neuroimmunology Group, Department of Neurology (S.J., B.W.), University of Heidelberg, Germany; Department of Neurology (P.R.), Medical University of Vienna, Austria; Institute of Neuropathology (M.S.W.) and Department of Neurology (M.S.W., H.P., P.K.), University Medical Center Göttingen; Department of Neurology (L.R., C.G.), Jena University Hospital; Neuroimmunological Section, Department of Neurology (N.R., U.Z.), University of Rostock; Department of Neurology (M.D., L.K.), University of Münster; Department of Neurology and Institute of Neuroimmunology and MS (K.Y., J.-P.S.), University Medical Center Hamburg-Eppendorf; Department of Neurology (M.K., P.K.), Nordwest-Hospital Sanderbusch, Sande; Department of Neurology (W.M.), Helios Hanseklinikum Stralsund; Department of Neurology (F.L., H.T.), University of Ulm, Germany; and Faculty of Medicine and Health Sciences (A.K.), Macquarie University, Sydney, New South Wales, Australia.
² From the Department of Neurology, Medical Faculty (M.R., J. Harmel, J.G., H.-P.H., O.A., P.A.), and Department of Neurology, Center for Neurology and Neuropsychiatry, LVR-Klinikum (M.R.), Heinrich Heine University Düsseldorf; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (H.Z., A.U.B., F.P.), Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, and Max Delbrueck Center for Molecular Medicine, Germany; Department of Neurology (A.U.B.), University of California Irvine; Department of Neurology (A.H., M.B.), University of Würzburg; Department of Neurology (M.B.), Caritas Hospital, Bad Mergentheim; Clinical Neuroimmunology and Neurochemistry (M.W.H.), Department of Neurology (C.T.), Hannover Medical School; Department of Neurology (C.S., I.A., I.K., K.H.), St. Josef Hospital, Ruhr University Bochum, Germany; Department of Neurology (I.A.), Sechenov First Moscow State Medical University, Moscow, Russia; Marianne-Strauß-Klinik (I.K.), Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke, Berg; Institute of Clinical Neuroimmunology (J. Halva, T.K., H.P.), University Hospital, Ludwig-Maximilians University, Munich; Molecular Neuroimmunology Group, Department of Neurology (S.J., B.W.), University of Heidelberg, Germany; Department of Neurology (P.R.), Medical University of Vienna, Austria; Institute of Neuropathology (M.S.W.) and Department of Neurology (M.S.W., H.P., P.K.), University Medical Center Göttingen; Department of Neurology (L.R., C.G.), Jena University Hospital; Neuroimmunological Section, Department of Neurology (N.R., U.Z.), University of Rostock; Department of Neurology (M.D., L.K.), University of Münster; Department of Neurology and Institute of Neuroimmunology and MS (K.Y., J.-P.S.), University Medical Center Hamburg-Eppendorf; Department of Neurology (M.K., P.K.), Nordwest-Hospital Sanderbusch, Sande; Department of Neurology (W.M.), Helios Hanseklinikum Stralsund; Department of Neurology (F.L., H.T.), University of Ulm, Germany; and Faculty of Medicine and Health Sciences (A.K.), Macquarie University, Sydney, New South Wales, Australia. phil.albrecht@gmail.com.

PMID: 31796527
DOI: 10.1212/WNL.0000000000008684

Abstract

Objective: To investigate if patients with neuromyelitis optica spectrum disorder (NMOSD) develop subclinical visual pathway impairment independent of acute attacks.

Methods: A total of 548 longitudinally assessed full-field visual evoked potentials (VEP) of 167 patients with NMOSD from 16 centers were retrospectively evaluated for changes of P100 latencies and P100-N140 amplitudes. Rates of change in latencies (RCL) and amplitudes (RCA) over time were analyzed for each individual eye using linear regression and compared using generalized estimating equation models.

Results: The rates of change in the absence of optic neuritis (ON) for minimal VEP intervals of ≥3 months between baseline and last follow-up were +1.951 ms/y (n = 101 eyes; SD = 6.274; p = 0.012) for the P100 latencies and -2.149 µV/y (n = 64 eyes; SD = 5.013; p = 0.005) for the P100-N140 amplitudes. For minimal VEP intervals of ≥12 months, the RCL was +1.768 ms/y (n = 59 eyes; SD = 4.558; p = 0.024) and the RCA was -0.527 µV/y (n = 44 eyes; SD = 2.123; p = 0.111). The history of a previous ON >6 months before baseline VEP had no influence on RCL and RCA. ONs during the observational period led to mean RCL and RCA of +11.689 ms/y (n = 16 eyes; SD = 17.593; p = 0.003) and -1.238 µV/y (n = 11 eyes; SD = 3.708; p = 0.308), respectively.

Conclusion: This first longitudinal VEP study of patients with NMOSD provides evidence of progressive VEP latency delay occurring independently of acute ON. Prospective longitudinal studies are needed to corroborate these findings and help to interpret the clinical relevance.

MeSH terms

Adult
Evoked Potentials, Visual / physiology*
Female
Humans
Longitudinal Studies
Male
Neuromyelitis Optica / complications
Neuromyelitis Optica / physiopathology*
Optic Neuritis / etiology