Forschungsschwerpunkt Neuromyelitis optica-Spektrum-Erkrankungen (NMOSD)
NEUROMYELITIS OPTICA SPECTRUM DISORDERS (NMOSD)
Diagnostic and pathophysiological relevance of autoantibodies to aquaporin-4
Principal investigators: Sven Jarius, Brigitte Wildemann
Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system that predominantly affects the optic nerves and the spinal cord and which was long considered a variant of multiple sclerosis. Our work focuses on investigating the diagnostic, prognostic, und pathophysiological relevance of autoantibodies to the water channel protein aquaporin-4 (termed NMO-IgG or AQP4-IgG) and of autoantibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) in patients with neuromyelitis optica (NMO) and related syndromes (longitudinally extensive transverse myelitis, recurrent optic neuritis, brainstem encephalitis) and on developing and establishing new, recombinant assays for the detection of NMO-IgG/AQP4-IgG and MOG-IgG.
Independent projects are dedicated to investigating the pathophysiological and diagnostic relevance of autoantibodies in other inflammatory diseases of the central and peripheral nervous system (e.g., MOG encephalomyelitis, multiple sclerosis, paraneoplastic and non-paraneoplastic cerebellar ataxia, limbic encephalitis, peripheral neuropathy, Susac syndrome; see here and here).
Email:
sven.jarius(at)med.uni-heidelberg.de
brigitte.wildemann(at)med.uni-heidelberg.de
Selected publications
- Jarius S, Aktas O, Ayzenberg I, Bellmann-Strobl J, Berthele A, Giglhuber K, Häußler V, Havla J, Hellwig K, Hümmert MW, Kleiter I, Klotz L, Krumbholz M, Kümpfel T, Paul F, Ringelstein M, Ruprecht K, Senel M, Stellmann JP, Bergh FT, Tumani H, Wildemann B, Trebst C; Neuromyelitis Optica Study Group (NEMOS). Update on the diagnosis and treatment of neuromyelits optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part I: Diagnosis and differential diagnosis. J Neurol. 2023 Jul;270(7):3341-3368.
- Hümmert MW, Stern C, Paul F, Duchow A, Bellmann-Strobl J, Ayzenberg I, Schwake C, Kleiter I, Hellwig K, Jarius S, Wildemann B, Senel M, Berthele A, Giglhuber K, Luessi F, Grothe M, Klotz L, Schülke R, Gingele S, Faiss JH, Walter A, Warnke C, Then Bergh F, Aktas O, Ringelstein M, Stellmann JP, Häußler V, Havla J, Pellkofer H, Kümpfel T, Kopp B, Trebst C. Cognition in patients with neuromyelitis optica spectrum disorders: A prospective multicentre study of 217 patients (CogniNMO-Study). Mult Scler. 2023 Jun;29(7):819-831.
- Schwake C, Pakeerathan T, Kleiter I, Ringelstein M, Aktas O, Korporal-Kuhnke M, Wildemann B, Jarius S, Bayas A, Pul R, Ceylan U, Faissner S, Hellwig K, Ayroza Galvao Ribeiro Gomes AB, Lipps P, Pröbstel AK, Kümpfel T, Oswald E, Then Bergh F, Gödel C, Hümmert MW, Trebst C, Gold R, Ayzenberg I. Humoral COVID-19 vaccine response in patients with NMOSD/MOGAD during anti-IL-6 receptor therapy compared to other immunotherapies. Mult Scler 2023 Feb 7:13524585221151124.
- Hümmert MW, Bütow F, Tkachenko D, Ayzenberg I, Pakeerathan T, Hellwig K, Klotz L, Häußler V, Stellmann JP, Warnke C, Goereci Y, Etgen T, Luessi F, Bronzlik P, Gingele S, Lauenstein AS, Kleiter I, Rommer PS, Paul F, Bellmann-Strobl J, Duchow A, Then Bergh F, Pul R, Walter A, Pellkofer H, Kümpfel T, Pompsch M, Kraemer M, Albrecht P, Aktas O, Ringelstein M, Senel M, Giglhuber K, Berthele A, Jarius S, Wildemann B, Trebst C; Neuromyelitis Optica Study Group (NEMOS). Effects of the COVID-19 pandemic on patients with NMO spectrum disorders and MOG-antibody-associated diseases: COPANMO(G) study. Neurol Neuroimmunol Neuroinflamm 2023 Jan 24;10(2):e200082.
- Schindler P, Aktas O, Ringelstein M, Wildemann B, Jarius S, Paul F, Ruprecht K. Glial fibrillary acidic protein as a biomarker in neuromyelitis optica spectrum disorder: a current review. Expert Rev Clin Immunol 2023 Jan;19(1):71-91.
- Schroeder-Castagno M, Del Rio-Serrato A, Wilhelm A, Romero-Suárez S, Schindler P, Alvarez-González C, Duchow AS, Bellmann-Strobl J, Ruprecht K, Hastermann M, Grütz G, Wildemann B, Jarius S, Schmitz-Hübsch T, Paul F, Infante-Duarte C. Impaired response of blood neutrophils to cell-death stimulus differentiates AQP4-IgG-seropositive NMOSD from MOGAD. J Neuroinflammation 2022 Oct 1;19(1):239.
- Lin TY, Schindler P, Grittner U, Oertel FC, Lu A, Motamedi S, Yadav SK, Duchow AS, Jarius S, Kuhle J, Benkert P, Brandt AU, Bellmann-Strobl J, Schmitz-Hübsch T, Paul F, Ruprecht K, Zimmermann HG. Serum glial fibrillary acidic protein correlates with retinal structural damage in aquaporin-4 antibody positive neuromyelitis optica spectrum disorder. Mult Scler Relat Disord 2022 Aug 9;67:104100.
- Mewes D, Kuchling J, Schindler P, Khalil AAA, Jarius S, Paul F, Chien C. Diagnosis of neuromyelitis optica spectrum disorder (NMOSD) and MOG antibody-associated disease (MOGAD). Klin Monbl Augenheilkd 2022 Nov;239(11):1315-1324.
- Hümmert MW, Schöppe LM, Bellmann-Strobl J, Siebert N, Paul F, Duchow A, Pellkofer H, Kümpfel T, Havla J, Jarius S, Wildemann B, Berthele A, Bergh FT, Pawlitzki M, Klotz L, Kleiter I, Stangel M, Gingele S, Weber MS, Faiss JH, Pul R, Walter A, Zettl UK, Senel M, Stellmann JP, Häußler V, Hellwig K, Ayzenberg I, Aktas O, Ringelstein M, Schreiber-Katz O, Trebst C; Neuromyelitis Optica Study Group (NEMOS). Costs and Health-Related Quality of Life in Patients With NMO Spectrum Disorders and MOG-Antibody-Associated Disease: CHANCENMO Study. Neurology 2022 Mar 15;98(11):e1184-e1196.
- Ringelstein M, Ayzenberg I, Lindenblatt G, Fischer K, Gahlen A, Novi G, Hayward-Könnecke H, Schippling S, Rommer PS, Kornek B, Zrzavy T, Biotti D, Ciron J, Audoin B, Berthele A, Giglhuber K, Zephir H, Kümpfel T, Berger R, Röther J, Häußler V, Stellmann JP, Whittam D, Jacob A, Kraemer M, Gueguen A, Deschamps R, Bayas A, Hümmert MW, Trebst C, Haarmann A, Jarius S, Wildemann B, Grothe M, Siebert N, Ruprecht K, Paul F, Collongues N, Marignier R, Levy M, Karenfort M, Deppe M, Albrecht P, Hellwig K, Gold R, Hartung HP, Meuth SG, Kleiter I, Aktas O; Neuromyelitis Optica Study Group (NEMOS). Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG-Associated Disease and Neuromyelitis Optica Spectrum Disorders. Neurol Neuroimmunol Neuroinflamm. 2021 Nov 16;9(1):e1100.
- Ayzenberg I, Richter D, Henke E, Asseyer S, Paul F, Trebst C, Hümmert MW, Havla J, Kümpfel T, Ringelstein M, Aktas O, Wildemann B, Jarius S, Häußler V, Stellmann JP, Senel M, Klotz L, Pellkofer HL, Weber MS, Pawlitzki M, Rommer PS, Berthele A, Wernecke KD, Hellwig K, Gold R, Kleiter I; NEMOS (Neuromyelitis Optica Study Group). Pain, Depression, and Quality of Life in Neuromyelitis Optica Spectrum Disorder: A Cross-Sectional Study of 166 AQP4 Antibody-Seropositive Patients. Neurol Neuroimmunol Neuroinflamm 2021 Apr 20;8(3):e985.
- Pache F, Ringelstein M, Orhan A, Kleiter I, Jarius S, Siebert N, Bellmann-Strobl J, Paul F, Ruprecht K. C3 and C4 complement levels in AQP4-IgG-positive NMOSD and in MOGAD. J Neuroimmunol 2021; 360:577699.
- Abboud H, Salazar-Camelo A, George N, Planchon SM, Matiello M, Mealy MA, Goodman A; On-behalf of the Guthy-Jackson Foundation NMO International Clinical Consortium. Symptomatic and restorative therapies in neuromyelitis optica spectrum disorders. J Neurol 2022 Apr;269(4):1786-1801.
- Schindler P, Grittner U, Oechtering J, Leppert D, Siebert N, Duchow AS, Oertel FC, Asseyer S, Kuchling J, Zimmermann HG, Brandt AU, Benkert P, Reindl M, Jarius S, Paul F, Bellmann-Strobl J, Kuhle J, Ruprecht K. Serum GFAP and NfL as disease severity and prognostic biomarkers in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder. J Neuroinflammation 2021 May 1;18(1):105.
- Jarius S, Wildemann B. [Aquaporin 4 antibody-positive neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis. A brief review]. Nervenarzt 2021 Apr;92(4):317-333.
- Jarius S, Paul F, Weinshenker BG, Levy M, Kim HJ, Wildemann B. Neuromyelitis optica. Nature Reviews Disease Primers 2020 Oct 22;6(1):85. [FULL LINK] [READ ONLY (FREE)]
- Mao-Draayer Y, Thiel S, Mills E, Chitnis T, Fabian M, Katz Sand I, Leite MI, Jarius S, Hellwig K. Neuromyelitis optica spectrum disorders and pregnancy: therapeutic considerations. Nature Reviews Neurology 2020 Mar;16(3):154-170.
- Wildemann B, Horstmann S, Korporal-Kuhnke M, Viehöver A, Jarius S. AQP4- und MOG-Antikörper-assoziierte Optikusneuritis: Diagnose und Therapie. Klin Monbl Augenheilkd 2020 Nov;237(11):1290-1305.
- Wingerchuk DM, Fujihara K, Palace J, Berthele A, Levy M, Kim HJ, Nakashima I, Oreja-Guevara C, Wang KC, Miller L, Shang S, Sabatella G, Yountz M, Pittock SJ; PREVENT Study Group. Long-Term Safety and Efficacy of Eculizumab in Aquaporin-4 IgG-Positive NMOSD. Ann Neurol 2021 Jun;89(6):1088-1098.
- Schmidt FA, Chien C, Kuchling J, Bellmann-Strobl J, Ruprecht K, Siebert N, Asseyer S, Jarius S, Brandt AU, Scheel M, Paul F. Differences in advanced magnetic resonance imaging in MOG-IgG and AQP4-IgG seropositive neuromyelitis optica spectrum disorders: a comparative study. Front Neurol 2020 Sep 30;11:499910.
- Juenger V, Cooper G, Chien C, Chikermane M, Oertel FC, Zimmermann H, Ruprecht K, Jarius S, Siebert N, Kuchling J, Papadopoulou A, Asseyer S, Bellmann-Strobl J, Paul F, Brandt AU, Scheel M. Optic chiasm measurements may be useful markers of anterior optic pathway degeneration in neuromyelitis optica spectrum disorders. Eur Radiol 2020 Sep;30(9):5048-5058.
- Tenembaum S, Yeh EA; Guthy-Jackson Foundation International Clinical Consortium (GJCF-ICC). Pediatric NMOSD: A Review and Position Statement on Approach to Work-Up and Diagnosis. Front Pediatr 2020 Jun 25;8:339.
- Gastaldi M, Todisco M, Carlin G, Scaranzin S, Zardini E, Minafra B, Zangaglia R, Pichiecchio A, Reindl M, Jarius S, Pacchetti C, Franciotta D. AQP4 autoantibodies in patients with idiopathic normal pressure hydrocephalus. J Neuroimmunol 2020 Dec 15;349:577407.
- Jarius S, Wildemann B. The history of neuromyelitis optica. Part 2: 'Spinal amaurosis', or how it all began. J Neuroinflammation 2019;16(1):280. [FREE PDF]
- Ringelstein M, Harmel J, Zimmermann H, Brandt AU, Paul F, Haarmann A, Buttmann M, Hümmert MW, Trebst C, Schroeder C, Ayzenberg I, Kleiter I, Hellwig K, Havla J, Kümpfel T, Jarius S, Wildemann B, Rommer P, Weber M, Pellkofer H, Röpke L, Geis C, Retzlaff N, Zettl U, Deppe M, Klotz L, Young K, Stellmann JP, Kaste M, Kermer P, Marouf W, Lauda F, Tumani H, Graf J, Klistorner S, Hartung HP, Aktas O, Albrecht P. Author response: Longitudinal optic neuritis-unrelated visual evoked potential changes in NMO spectrum disorders. Neurology 2020 Sep 29;95(13):610.
- Ringelstein M, Harmel J, Zimmermann H, Brandt AU, Paul F, Haarmann A, Buttmann M, Hümmert MW, Trebst C, Schroeder C, Ayzenberg I, Kleiter I, Hellwig K, Havla J, Kümpfel T, Jarius S, Wildemann B, Rommer PS, Weber M, Pellkofer H, Röpke L, Geis C, Retzlaff N, Zettl UK, Deppe M, Klotz L, Young KL, Stellmann JP, Kaste M, Kermer P, Marouf W, Lauda F, Tumani H, Graf J, Klistorner A, Hartung HP, Aktas O, Albrecht P. Longitudinal optic neuritis-unrelated visual evoked potential changes in NMO spectrum disorders. Neurology 2020 Jan 28;94(4):e407-e418.
- Ringelstein M, Harmel J, Zimmermann H, Brandt AU, Paul F, Haarmann A, Buttmann M, Hümmert MW, Trebst C, Schroeder C, Ayzenberg I, Kleiter I, Hellwig K, Havla J, Kümpfel T, Jarius S, Wildemann B, Rommer P, Weber M, Pellkofer H, Röpke L, Geis C, Retzlaff N, Zettl U, Deppe M, Klotz L, Young K, Stellmann JP, Kaste M, Kermer P, Marouf W, Lauda F, Tumani H, Graf J, Klistorner S, Hartung HP, Aktas O, Albrecht P. Author response: Longitudinal optic neuritis-unrelated visual evoked potential changes in NMO spectrum disorders. Neurology 2020 Sep 29;95(13):610.
- Jarius S, Wildemann B. Devic's index case: A critical reappraisal - AQP4-IgG-mediated neuromyelitis optica spectrum disorder, or rather MOG encephalomyelitis? J Neurol Sci 2019 Dec 15;407:116396.
- Kleiter I, Gahlen A, Borisow N, Fischer K, Wernecke KD, Hellwig K, Pache F, Ruprecht K, Havla J, Kümpfel T, Aktas O, Hartung HP, Ringelstein M, Geis C, Kleinschnitz C, Berthele A, Hemmer B, Angstwurm K, Stellmann JP, Schuster S, Stangel M, Lauda F, Tumani H, Mayer C, Krumbholz M, Zeltner L, Ziemann U, Linker R, Schwab M, Marziniak M, Then Bergh F, Hofstadt-van Oy U, Neuhaus O, Zettl UK, Faiss J, Wildemann B, Paul F, Jarius S, Trebst C; NEMOS (Neuromyelitis Optica Study Group). Apheresis therapies for NMOSD attacks: A retrospective study of 207 therapeutic interventions. Neurol Neuroimmunol Neuroinflamm 2018 Sep 26;5(6):e504.
- Jarius S, Wuthenow AB, Wildemann B. The first Japanese report on neuromyelitis optica rediscovered: acute bilateral blindness, tetraparesis and respiratory insufficiency in a 35-year-old man (1891). J Neurol Sci 2018 Dec 15;395:121-125.
- Oertel et al. Retinal Ganglion Cell Loss in Neuromyelitis Optica: A Longitudinal Study. J Neurol Neurosurg Psychiatry. 2018 Dec;89(12):1259-1265.
- Pache F, Wildemann B, Paul F, Jarius S. Neuromyelitis optica. Neuroradiol Scan 2018; 8(2):159-181.
- Asgari N, Jarius S, Laustrup H, Skejoe HP, Lillevang ST, Weinshenker BG, Voss A. Aquaporin-4-autoimmunity in patients with systemic lupus erythematosus: A predominantly population-based study. Mult Scler 2018 Mar;24(3):331-339.
- Gahlen A, Trampe AK, Haupeltshofer S, Ringelstein M, Aktas O, Berthele A, Wildemann B, Gold R, Jarius S, and Kleiter I. Aquaporin-4-antibodies in patients treated with natalizumab for suspected multiple sclerosis. Neurology: Neuroimmunology & Neuroinflammation 2017;4:e363.
- Stellmann JP, Krumbholz M, Friede T, Gahlen A, Borisow N, Fischer K, Hellwig K, Pache F, Klemens R, Havla J, Kümpfel T, Aktas O, Hartung HP, Ringelstein M, Geis C, Kleinschnitz C, Berthele A, Hemmer B, Angstwurm K, Young KL, Schuster S, Stangel M, Lauda F, Tumani H, Mayer C, Zeltner L, Ziemann U, Linker RA, Schwab M, Marziniak M, Then Bergh F, Hofstadt-van Oy U, Neuhaus O, Zettl U, Faiss J, Wildemann B, Paul F, Jarius S, Trebst C, Kleiter I; on behalf of NEMOS (Neuromyelitis Optica Study Group). Immunotherapies in neuromyelitis optica spectrum disorder: Efficacy and predictors of response. JNNP 2017 Aug;88(8):639-647.
- Pache F, Wildemann B, Paul F, Jarius S. Neuromyelitis optica. Fortschr Neurol Psychiatr 2017 Feb;85(2):100-114.
- Jarius S, Ruprecht K, Kleiter I, Borisow N, Asgari N, Pitarokoili K, Pache F, Stich O, Beume L, Hümmert MW, Trebst C, Ringelstein M, Aktas O, Winkelmann A, Buttmann M, Schwarz A, Zimmermann H, Brandt AU, Franciotta D, Capobianco M, Kuchling J, Haas J, Korporal-Kuhnke M, Lillevang ST, Fechner K, Schanda K, Paul F*, Wildemann B*, Reindl M*. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin. J Neuroinflammation 2016 Okt 26;13(1):279. [FREE PDF]
- Jarius S, Ruprecht K, Kleiter I, Borisow N, Asgari N, Pitarokoili K, Pache F, Stich O, Beume L, Hümmert MW, Ringelstein M, Trebst C, Winkelmann A, Schwarz A, Buttmann M, Zimmermann H, Kuchling J, Franciotta D, Capobianco M, Siebert E, Lukas C, Korporal-Kuhnke M, Haas J, Fechner K, Brandt AU, Schanda K, Aktas O, Paul F*, Reindl M*, Wildemann B*. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment, and long-term outcome. J Neuroinflammation 2016 Okt 27;13(1):280. [FREE PDF]
- Jarius S, Kleiter I, Ruprecht K, Asgari N, Pitarokoili K, Borisow N, Hümmert MW, Trebst C, Pache F, Winkelmann A, Beume LA, Ringelstein M, Stich O, Aktas O, Korporal-Kuhnke M, Schwarz A, Lukas C, Haas J, Fechner K, Buttmann M, Bellmann-Strobl J, Zimmermann H, Brandt AU, Franciotta D, Schanda K, Paul F*, Reindl M*, Wildemann B*. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 3: Brainstem involvement – frequency, presentation and outcome. J Neuroinflammation 2016 Nov 1;13:281. [FREE PDF]
- Pache F, Zimmermann H, Mikolajczak J, Schumacher S, Lacheta A, Oertel FC, Bellmann-Strobel J, Jarius S, Wildemann B, Reindl M, Waldman A, Soelberg K, Nasrin Asgari, Ringelstein M, Aktas O, Gross N, Buttmann M, Ach T, Ruprecht K, Paul F, Brandt AU. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 4: Afferent visual system damage after optic neuritis in MOG-IgG-seropositive versus AQP4-IgG-seropositive patients. J Neuroinflammation 2016 Nov 1;13:282. [FREE PDF]
- Borisow N, Kleiter I, Gahlen A, Fischer K, Wernecke KD, Pache F, Ruprecht K, Havla J, Krumbholz M, Kümpfel T, Aktas O, Ringelstein M, Geis C, Kleinschnitz C, Berthele A, Hemmer B, Angstwurm K, Weissert R, Stellmann JP, Schuster S, Stangel M, Lauda F, Tumani H, Mayer C, Zeltner L, Ziemann U, Linker RA, Schwab M, Marziniak M, Then Bergh F, Hofstadt-van Oy U, Neuhaus O, Winkelmann A, Marouf W, Rückriem L, Faiss J, Wildemann B, Paul F, Jarius S, Trebst C, Hellwig K; on behalf of NEMOS (Neuromyelitis Optica Study Group). Influence of female sex and fertile age on neuromyelitis optica spectrum disorders. Mult Scler 2017; Jul;23(8):1092-1103.
- Waters P, Reindl M, Saiz A, Schanda K, Tuller F, Kral V, Nytrova P, Sobek O, Nielsen HH, Barington T, Lillevang ST, Illes Z, Rentzsch K, Berthele A, Berki T, Granieri L, Bertolotto A, Giometto B, Zuliani L, Hamann D, van Pelt ED, Hintzen R, Höftberger R, Costa C, Comabella M, Montalban X, Tintoré M, Siva A, Altintas A, Deniz G, Woodhall M, Palace J, Paul F, Hartung HP, Aktas O, Jarius S, Wildemann B, Vedeler C, Ruiz A, Leite MI, Trillenberg P, Probst M, Saschenbrecker S, Vincent A, Marignier R. Multicentre comparison of a diagnostic assay: aquaporin-4 antibodies in neuromyelitis optica. J Neurol Neurosurg Psychiatry 2016 Sep;87(9):1005-15.
- Ayzenberg I, Schollhammer J, Hoepner R, Hellwig K, Ringelstein M, Aktas O, Kümpfel T, Krumbholz M, Trebst C, Paul F, Pache F, Obermann M, Zeltner L, Schwab M, Berthele A, Jarius S, Kleiter I, on behalf of the Neuromyelitis Optica Study Group (NEMOS). Efficacy of glatiramer acetate in neuromyelitis optica spectrum disorder: a multicenter retrospective study. J Neurol 2016 Mar;263(3):575-82.
- Metz I, Beißbarth T, Ellenberger D, Pache F, Stork L, Ringelstein M, Aktas O, Jarius S, Wildemann B, Dihazi H, Friede T, Brück W, Ruprecht K, Paul F. Serum peptide reactivities may distinguish neuromyelitis optica subgroups and multiple sclerosis. Neurology: Neuroimmunology & Neuroinflammation 2016 Feb 2;3(2):e204.
- Kleiter I, Gahlen A, Borisow N, Fischer K, Wernecke K, Wegner B, Hellwig K, Pache F, Ruprecht K, Havla J, Krumbholz M, Kümpfel T, Aktas O, Hartung HP, Ringelstein M, Geis C, Kleinschnitz C, Berthele A, Hemmer B, Angstwurm K, Stellmann JP, Schuster S, Stangel M, Lauda F, Tumani H, Mayer C, Zeltner L, Ziemann U, Linker R, Schwab M, Marziniak M, ThenBergh F, Hofstadt-van Oy U, Neuhaus O, Winkelmann A, Marouf W, Faiss J, Wildemann B, Paul F, Jarius S, Trebst C, on behalf of the Neuromyelitis optica Study Group (NEMOS). Neuromyelitis optica: evaluation of 871 attacks and 1153 treatment courses. Ann Neurol 2016 Feb;79(2):206-16.
- Keller A, Leidinger P, Meese E, Haas J, Backes C, Rasche L, Behrens JR, Pfuhl C, Wakonig K, Gieß RM, Jarius S, Meder B, Bellmann-Strobl J, Paul F, Pache FC, Ruprecht K. Next-generation sequencing identifies altered whole blood microRNAs in neuromyelitis optica spectrum disorder which may permit discrimination from multiple sclerosis. J Neuroinflammation 2015 Oct 31;12(1):196.
- Jarius S, Aktas O, Wildemann B. Gamma-aminobutyric receptor agonists, aquaporin-4, and neuromyelitis optica: a potential link. Med Hypotheses 2015 Nov;85(5):628-30.
- Jarius S, Wildemann B. Devic’s disease before Devic: Bilateral optic neuritis and simultaneous myelitis in a young woman (1874). J Neurol Sci 2015; Nov 15;358(1-2):419-21.
- Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peicoto M, Levy M, Simon JH, Tenembaum S, Traboulsee AL, Waters P, Wellik K, Weinshenker BG. International Consensus Diagnostic Criteria for Neuromyelitis Optica Spectrum Disorders. Neurology 2015 Jul 14;85(2):177-89.
- Melamed E, Levy M, Waters PJ, Sato DK, Bennett JL, John GR, Hooper DC, Saiz A, Bar-Or A, Kim HJ, Pandit L, Leite MI, Asgari N, Kissani N, Hintzen R, Marignier R, Jarius S, Marcelletti J, Smith TJ, Yeaman MR, Han MH. Update on biomarkers in neuromyelitis optica. Neurol Neuroimmunol Neuroinflamm 2015 Jul 23;2(4):e134.
- Krumbholz M, Hofstadt-van Oy U, Angstwurm K, Kleiter I, Jarius S, Paul F, Aktas O, Buchholz G, Kern P, Straube A, Kümpfel T. Very late-onset neuromyelitis optica spectrum disorder beyond the age of 75. J Neurol 2015 May;262(5):1379-84.
- Harmel J, Ringelstein M, Ingwersen J, Mathys C, Goebels N, Hartung HP, Jarius S, Aktas O. Interferon-β-related tumefactive brain lesion in a Caucasian patient with neuromyelitis optica and clinical stabilization with tocilizumab. BMC Neurology 2014;14:247.
- Jarius S, Paul F, Fechner K, Klemens R, Kleiter I, Franciotta D, Ringelstein M, Pache F, Aktas O, Wildemann B. Aquaporin-4 antibody testing: direct comparison of M1-AQP4-DNA-transfected cells with leaky scanning versus M23-AQP4-DNA-transfected cells as antigenic substrate. J Neuroinflammation 2014;11:129.
- Ringelstein M, Aktas O, Harmel J, Prayer D, Jarius S, Wildemann B, Hartung HP, Salhofer-Polanyi S, Leutmezer F, Rommer PS. [Contribution of spinal cord biopsy in the differential diagnosis of longitudinal extensive transverse myelitis]. Nervenarzt 2014 Oct;85(10):1298-303.
- Jarius S, Wildemann B, Paul F. Neuromyelitis optica: clinical features, immunopathogenesis and treatment. Clin Exp Immunol 2014 May;176(2):149-64.
- Waters PJ, Pittock SJ, Bennett JL, Jarius S, Weinshenker BG, Wingerchuk DM. Evaluation of aquaporin-4 antibody assays. Clin Exp Neuroimmunol 2014 Oct;5(3):290–303.
- Ringelstein M, Kleiter I, Ayzenberg I, Borisow N, Paul F, Ruprecht K, Kraemer M, Cohn E, Wildemann B, Jarius B, Hartung HP, Aktas O, Albrecht P. Visual evoked potentials in neuromyelitis optica and its spectrum disorders. Mult Scler 2014 Apr;20(5):617-20.
- Levy M*, Wildemann B*, Jarius S*, Orellano B, Sasidharan S, Weber M, Stüve O. Immunopathogenesis of neuromyelitis optica. Adv Immunol 2014;121:213–242.
- Jarius S, Wildemann B. 'Spinal amaurosis' (1841). On the early contribution of Edward Hocken to the concept of neuromyelitis optica. J Neurol 2014 Feb;261(2):400-4.
- von Glehn F, Jarius S, Cavalcanti Lira RP, Alves Ferreira MC, Ribeiro von Glehn FH, Costa e Castro SM, Beltramini GC, Bergo FPG, Farias AS, Brandão CO, Wildemann B, Damasceno BP, Cendes F, Santos LMB, Yasuda CL. Structural brain abnormalities are related to retinal nerve fiber layer thinning and disease duration in neuromyelitis optica spectrum disorders. Mult Scler 2014 Aug;20(9):1189-97.
- Trebst C, Jarius S, Berthele A, Paul F, Schippling S, Wildemann B, Borisow N, Kleiter I, Aktas O, Kümpfel T, Neuromyelitis Optica Study Group (NEMOS). Update on the diagnosis and treatment of neuromyelitis optica: Recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol 2014; Jan;261(1):1-16.
- Jarius S, Wildemann B. Aquaporin-4 antibodies (NMO-IgG) as a serological marker of neuromyelitis optica: a critical review of the literature. Brain Pathol 2013 Nov;23(6):661-83. FREE PDF
- Ringelstein M, Metz I, Ruprecht K, Koch A, Rappold J, Ingwersen J, Mathys C, Jarius S, Brück W, Hartung H-P, Paul F, Aktas O, for the Neuromyelitis Optica Study Group (NEMOS). Contribution of spinal cord biopsy to diagnosis of aquaporin-4 antibody positive neuromyelitis optica spectrum disorder. Mult Scler 2014 Jun;20(7):882-8.
- Collongues N, Marignier R, Jacob A, Leite M, Siva A, Paul F, Zephir H, Akman-Demir G, Elsone L, Jarius S, Papeix C, Mutch K, Saip S, Wildemann B, Kitley J, Karabudak R, Aktas O, Kuscu D, Altintas A, Palace J, Confavreux C, De Seze J. Characterization of neuromyelitis optica and neuromyelitis optica spectrum disorder patients with a late onset. Mult Scler 2013 Dec 9;20(8):1086-1094.
- Jarius S, Wildemann B. Aquaporin-4 antibodies, CNS acidosis and neuromyelitis optica: a potential link. Med Hypotheses 2013 Dec;81(6):1090-5.
- Kremer L, Mealy M, Jacob A, Nakashima I, Cabre P, Bigi S, Paul F, Jarius S, Aktas O, Elsone L, Mutch K, Levy M, Takai Y, Collongues N, Banwell B, Fujihara K, de Seze J. Brainstem manifestations in neuromyelitis optica: a multicenter study of 258 patients. Mult Scler 2014 Jun;20(7):843-7.
- Schmidt F, Goektas O, Jarius S, Wildemann B, Ruprecht K, Paul F, Harms L. Olfactory dysfunction in patients with neuromyelitis optica. Mult Scler Intern 2013, ID 654501.
- Schneider E, Zimmermann H, Oberwahrenbrock T, Kaufhold F, Kadas EM, Petzold A, Bilger F, Borisow N, Jarius S, Wildemann B, Ruprecht K, Brandt AU, Paul F. Optical coherence tomography reveals distinct patterns of retinal damage in neuromyelitis optica and multiple sclerosis. PLoS One 2013 Jun 21;8(6):e66151.
- Jarius S, Wildemann B. The history of neuromyelitis optica. J Neuroinflammation 2013 Jan 15;10:8.
- Wildemann B, Jarius S, Paul F. [Neuromyelitis optica]. Nervenarzt 2013 Apr;84(4):436-41.
- Jarius S, Wildemann B. An early British case of neuromyelitis optica (1850). BMJ 2012 Dec 22;345:e6430.
- Jarius S, Lauda F, Wildemann B, Tumani H. Steroid-responsive hearing impairment in NMO-IgG/aquaporin-4-antibody-positive neuromyelitis optica. J Neurology 2013 Feb;260(2):663-4.
- Jarius S, Paul F, Ruprecht K, Wildemann B. Low vitamin B12 levels and gastric parietal cell antibodies in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders. J Neurology 2012;259(12):2743-5.
- Jarius S, Franciotta D, Paul F, Bergamaschi R, Rommer PS, Ruprecht K, Ringelstein M, Aktas O, Kristoferitsch W, Wildemann B. Testing for antibodies to human aquaporin-4 by ELISA: Sensitivity, specificity, and direct comparison with immunohistochemistry. J Neurol Sci 2012 Sep 15;320(1-2):32-7.
- Jarius S, Wildemann B. On the contribution of Thomas Clifford Allbutt, FRS, to the early history of neuromyelitis optica. J Neurol 2013 Jan;260(1):100-4.
- von Glehn F, Jarius S, Penalva de Oliveira AC, Brandão CO, Farias AS, Damasceno A, Casseb J, Moraes AS, Longhini ALF, Wandinger KP, Damasceno DB, Wildemann B, Santos L. Aquaporin-4 antibodies are not related to HTLV-1 associated myelopathy. PLoS One 2012 Jul 10; 7(7):e39372.
- Granieri L, Marnetto F, Valentino P, Frau J, Patanella AK, Nytrova P, Sola P, Capobianco M, Jarius S, Bertolotto A. Evaluation of a multiparametric immunofluorescence assay for standardization of neuromyelitis optica serology. PLoS One. 2012;7(6):e38896.
- Sinnecker T, Dörr J, Pfueller CF, Harms L, Ruprecht K, Jarius S, Brück W, Niendorf T, Wuerfel J, Paul F. Distinct lesion morphology at 7T MRI differentiates neuromyelitis optica from multiple sclerosis. Neurology 2012 Aug 14;79(7):708-14.
- Jarius S, Ruprecht K, Wildemann B, Kuempfel T, Ringelstein M, Geis C, Kleiter I, Kleinschnitz C, Berthele A, Brettschneider J, Hellwig K, Hemmer B, Linker R, Lauda F, Mayer CA, Tumani H, Melms A, Trebst C, Stangel M, Marziniak M, Hoffmann F, Schippling S, Faiss J, Neuhaus O, Ettrich B, Zentner C, Guthke K, Hofstadt-van Oy U, Reuss R, Pellkofer H, Ziemann U, Kern P, Wandinger KP, Then Bergh F, Boettcher T, Langel S, Liebetrau M, Rommer PS, Niehaus S, Münch C, Winkelmann A, Zettl U, Metz I, Veauthier C, Sieb JP, Wilke C, Hartung HP, Aktas O, Paul F. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica. A multicentre study of 175 patients. J Neuroinflammation 2012; 9:14.
- Wildemann B, Jarius S, Paul F. Neuromyelitis optica. Akt Neurol 2012 Jan; 39: 33-41.
- Jarius S, Wildemann B. The case of the Marquis de Causan (1804): an early account of visual loss associated with spinal cord inflammation. J Neurol 2012 Jul; 259(7):1354-7.
- Leite MI, Coutinho E, Lana-Peixoto M, Apostolos S, Waters P, Sato D, Melamud L, Marta M, Graham A, Spillane J, Villa AM, Callegaro D, Santos E, Martins da Silva A, Jarius S, Howard R, Nakashima I, Giovannoni G, Buckley C, Hilton-Jones D, Vincent A, Palace J. Myasthenia gravis and neuromyelitis optica spectrum disorder: A multicenter study of 16 patients. Neurology 2012 May 15;78(20):1601-7.
- Jarius S, Paul F, Franciotta D, de Seze J, Münch C, Salvetti M, Ruprecht K, Liebetrau M, Wandinger KP, Akman-Demir G, Melms A, Kristoferitsch W, B Wildemann. Neuromyelitis optica spectrum disorders in patients with myasthenia gravis: ten new aquaporin-4 antibody positive cases and a review of the literature. Mult Scler 2012 Aug;18(8):1135-43.
- Jarius S, Wandinger KP, Borowski K, Stoecker W, Wildemann B. Antibodies to CV2/CRMP5 in neuromyelitis optica-like disease: Case report and review of the literature. Clin Neurol Neurosurg 2012 May;114(4):331-5.
- Mader S, Gredler V, Schanda K, Rostasy K, Dujmovic I, Pfaller K, Lutterotti A, Jarius S, Di Pauli F, Kuenz B, Ehling R, Hegen H, Deisenhammer F, Aboul-Enein F, Storch MK, Koson P, Drulovic J, Kristoferitsch W, Berger T, Reindl M. Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders. J Neuroinflammation 2011 Dec 28;8:184
- Jarius S, Wildemann B. 'Noteomielite' accompanied by acute amaurosis (1844). An early case of neuromyelitis optica. J Neurol Sci 2012 Feb;313(1–2):182–4.
- Jarius S, Wildemann B. Effect of storage conditions and freeze/thaw cycles on aquaporin-4 antibody (NMO-IgG) serum levels. Clin Chem Lab Med 2011 Sep 21;49(12):2121-2.
- Závada J, Nytrová P, Wandinger KP, Jarius S, Svobodová R, Probst C, Peterová V, Tegzová D, Pavelka K, and Vencovský J. Seroprevalence and specificity of NMO-IgG (anti-aquaporin 4 antibodies) in patients with neuropsychiatric systemic lupus erythematosus. Rheumat Int 2013 Jan;33(1):259-63; epub 29 Oct 2011.
- Jarius S, Paul F, Franciotta D, Ruprecht K, Ringelstein M, Rommer P, Bergamaschi R, Kleiter I, Stich O, Reuss R, Rauer S, Zettl UK, Wandinger KP, Melms A, Aktas O, Kristoferitsch W, Wildemann B. Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: results from 211 lumbar punctures. J Neurol Sci 2011 July 15;360(1-2):82-90.
- Jarius S, Jacobi C, de Seze J, Zephir H, Paul F, Franciotta D, Rommer P, Mader S, Kleiter I, Reindl M, Akman-Demir G, Seifert-Held T, Kristoferitsch W, Melms A, Wandinger KP, Wildemann B. Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders. Mult Scler 2011 Sep;17(9):1067-73.
- Jarius S, Wildemann B. An early case of neuromyelitis optica: On a forgotten report by Jacob Lockhart Clarke, FRS. Mult Scler 2011 Nov;17(11):1384-6.
- Trebst C, Berthele A, Jarius S, Kümpfel T, Schippling S, Wildemann B, Wilke C. Neuromyelitis optica Studiengruppe (NEMOS). [Diagnosis and treatment of neuromyelitis optica: Consensus recommendations of the Neuromyelitis Optica Study Group.] Nervenarzt 2011 Jun;82(6):768-77.
- Jarius S, Wandinger KP, Platzer S, Wildemann B. Homology between Klebsiella pneumoniae and human aquaporin-4: no evidence for cross-reactivity in neuromyelitis optica. A study on 114 patients. J Neurol 2011 May;258(5):929-31.
- Akman-Demir G, Tüzün E, Waters P, Içöz S, Kürtüncü M, Jarius S, Yapıcı Z, Mutlu M, Yeşilot N, Vincent A, Eraksoy M. Prognostic implications of aquaporin-4 antibody status in neuromyelitis optica patients. J Neurol 2011 Mar;258(3):464-70.
- Jarius S, Frederikson J, Waters P, Paul F, Akman-Demir G, Marignier R, Franciotta D, Ruprecht K, Kuenz B, Rommer P, Kristoferitsch W, Wildemann B, Vincent A. Frequency and prognostic impact of antibodies to aquaporin-4 in patients with optic neuritis. J Neurol Sci 2010 Nov 15;298(1-2):158-62.
- Editorial: Frequency and prognostic impact of antibodies to aquaporin-4 in patients with optic neuritis. Faculty of 1000 Prime, 19 Apr 2011 (doi: 10.3410/f.9750956.10441054).
- Jarius S, Franciotta D, Paul F, Ruprecht K, Bergamaschi R, Rommer PS, Reuss R, Probst C, Kristoferitsch W, Wandinger KP, Wildemann B. Cerebrospinal fluid antibodies to aquaporin-4 in neuromyelitis optica and related disorders: frequency, origin, and diagnostic relevance. J Neuroinflammation 2010 Sep 8;7:52.
- Jarius S, Wildemann B. AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance. Nat Rev Neurol 2010 Jul;6(7):383-92.
- Franciotta D, Di Stefano AL, Jarius S, Zardini E, Tavazzi E, Ballerini C, Marchioni E, Bergamaschi R, Ceroni M. Cerebrospinal BAFF and Epstein-Barr virus-specific oligoclonal bands in multiple sclerosis and other inflammatory demyelinating neurological diseases. J Neuroimmunol 2011 Jan;230(1-2):160-3.
- Jarius S, Warth A, Wandinger KP, Schnabel PA, Hoffmann H, Wildemann B, Muley T. Antibodies to aquaporin-4 in non-small cell lung cancer: a study on 50 patients. Neurol Sci 2010 Dec;31(6):871-2;31:871-2.
- Matiello M, Schaefer-Klein J, Brum DG, Atkinson EJ, Kantarci OH, Weinshenker BG; NMO genetics collaborators. HLA-DRB1*1501 tagging rs3135388 polymorphism is not associated with neuromyelitis optica. Mult Scler 2010 Aug;16(8):981-4.
- Mader S, Lutterotti A, Di Pauli F, Kuenz B, Schanda K, Aboul-Enein F, Khalil M, Storch MK, Jarius S, Kristoferitsch W, Berger T, Reindl M. Patterns of antibody binding to aquaporin-4 isoforms in neuromyelitis optica. PLoS One 2010 May 5;5(5):e10455.
- Jarius S, Franciotta D, Bergamaschi R, Wildemann B, Wandinger KP. Immunoglobulin M antibodies to aquaporin-4 in neuromyelitis optica and related disorders. Clin Chem Lab Med 2010 May;48(5):659-63.
- Wandinger KP, Stangel M, Witte T, Venables P, Charles P, Jarius S, Wildemann B, Probst C, Iking-Konert C, Schneider M. Autoantibodies against aquaporin-4 in patients with neuropsychiatric systemic lupus erythematosus and primary Sjogren's syndrome. Arthritis Rheum 2010 Apr;62(4):1198-200.
- Jarius S, Probst C, Borowski K, Franciotta D, Wildemann B, Stoecker W, Wandinger KP. Standardized method for the detection of antibodies to aquaporin-4 based on a highly sensitive immunofluorescence assay employing recombinant target antigen. J Neurol Sci 2010 Apr 15;291(1-2):52-6.
- Reuss R, Rommer PS, Brück W, Jarius S, Bolz M, and Zettl UK. Anti-AQP4 ab might be relevant in pregnancy. BMJ 2010 Feb 8; reply
- Reuss R, Rommer PS, Bruck W, Paul F, Bolz M, Jarius S, Boettcher T, Grossmann A, Bock A, Zipp F, Benecke R, Zettl UK. A woman with acute myelopathy in pregnancy: case outcome. BMJ 2009 Dec 10;339:b4026.
- Reuss R, Rommer PS, Bruck W, Paul F, Bolz M, Jarius S, Boettcher T, Grossmann A, Bock A, Zipp F, Benecke R, Zettl UK. A woman with acute myelopathy in pregnancy: case progression. BMJ 2009 Nov 19;339:b4025.
- Reuss R, Rommer PS, Bruck W, Paul F, Bolz M, Jarius S, Boettcher T, Grossmann A, Bock A, Zipp F, Benecke R, Zettl UK. A woman with acute myelopathy in pregnancy: case presentation. BMJ 2009 Nov 12;339:b3862.
- Bergamaschi R, Jarius S, Robotti M, Pichiecchio A, Wildemann B, Meola G. Two cases of benign neuromyelitis optica in patients with celiac disease. J Neurol 2009 Dec;256(12):2097-9.
- Jarius S, Aboul-Enein F, Waters P, Kuenz B, Hauser A, Berger T, Lang W, Reindl M, Vincent A, Kristoferitsch W. Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. Brain 2008 Nov;131(Pt 11):3072-80.
- Editorial: Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. J Neurol. 2008;255:1990-1992.
- Heerlein K, Jarius S, Jacobi C, Rohde S, Storch-Hagenlocher B, Wildemann B. Aquaporin-4 antibody positive longitudinally extensive transverse myelitis following varicella zoster infection. J Neurol Sci 2009 Jan 15;276(1-2):184-6.
- Jarius S, Jacob S, Waters P, Jacob A, Littleton E, Vincent A. Neuromyelitis optica in patients with gluten sensitivity associated with antibodies to aquaporin-4. J Neurol Neurosurg Psychiatry 2008 Sep;79(9):1084.
- Kay CS, Scola RH, Lorenzoni PJ, Jarius S, Arruda WO, Werneck LC. NMO-IgG positive neuromyelitis optica in a patient with myasthenia gravis but no thymectomy. J Neurol Sci 2008 Dec 15;275(1-2):148-50.
- Waters P, Jarius S, Littleton E, Leite MI, Jacob S, Gray B, Geraldes R, Vale T, Jacob A, Palace J, Maxwell S, Beeson D, Vincent A. Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis. Arch Neurol 2008 Jul;65(7):913-9.
- Paul F, Jarius S, Glumm R, Wildemann B, Zipp F, Aktas O. [Recent findings in pathogenesis, diagnostics and therapy of neuromyelitis optica]. Dtsch Med Wochenschr 2008 May;133(21):1125-9.
- Jarius S, Paul F, Franciotta D, Waters P, Zipp F, Hohlfeld R, Vincent A, Wildemann B. Mechanisms of disease: aquaporin-4 antibodies in neuromyelitis optica. Nature Clin Pract Neurol 2008 Apr;4(4):202-14.
- Jarius S, Franciotta D, Bergamaschi R, Rauer S, Wandinger KP, Petereit HF, Maurer M, Tumani H, Vincent A, Eichhorn P, Wildemann B, Wick M, Voltz R. Polyspecific, antiviral immune response distinguishes multiple sclerosis and neuromyelitis optica. J Neurol Neurosurg Psychiatry 2008 Oct;79(10):1134-6.
- Editorial: MRZ reaction could distinguish patients with NMO from those with MS. Nature Clin Pract Neurol. 2008;4:524.
- Franciotta D, Jarius S, Aloisi F. More on multiple sclerosis and neuromyelitis optica. Arch Neurol 2007 Dec;64(12):1802.
- Jarius S, Wildemann B. [Neuromyelitis optica]. Nervenarzt. 2007 Dec;78(12):1365-77.
- Jarius S, Paul F, Franciotta D, Wildemann B. Neuromyelitis optica. Curr Topics in Neuroimm 2007, p. 27-31.
- Jarius S, Paul F, Franciotta D, Aktas O, Hohlfeld R, Zipp F, Vincent A. Revised diagnostic criteria for neuromyelitis optica-incorporation of NMO-IgG status. Nature Clin Pract Neurol 2007 May;3(5):E1.
- Paul F*, Jarius S*, Aktas O, Bluthner M, Bauer O, Appelhans H, Franciotta D, Bergamaschi R, Littleton E, Palace J, Seelig HP, Hohlfeld R, Vincent A, Zipp F. Antibody to aquaporin 4 in the diagnosis of neuromyelitis optica. PLoS Med 2007 Apr;4(4):e133.
- Jarius S, Franciotta D, Bergamaschi R, Wright H, Littleton E, Palace J, Hohlfeld R, Vincent A. NMO-IgG in the diagnosis of neuromyelitis optica. Neurology 2007 Mar 27;68(13):1076-7.
- Kleiter I, Hellwig K, Berthele A, Kümpfel T, Linker RA, Hartung HP, Paul F, Aktas O; Neuromyelitis Optica Study Group. Failure of natalizumab to prevent relapses in neuromyelitis optica. Arch Neurol 2012 Feb;69(2):239-45.