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Headache in the course of multiple sclerosis: a prospective study

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

Multiple sclerosis (MS) is the most common immune-mediated inflammatory disease of the central nervous system (CNS). Early diagnosis and treatment is important to prevent progression of disability in the course of the chronic disease. Therefore, correct and fast identification of early symptoms is vital. Headache is generally not recognized as an early symptom of MS, although numerous studies could show a high prevalence of headache in MS patients. The most common misdiagnosis is migraine. The aim of this study is to investigate the prevalence as well as the phenomenology of headache in MS especially with regard to the progression of the disease. In a prospective, multicenter study, we unbiasedly recruited 150 patients with manifest MS based on the criteria of McDonald. 50 patients at the timepoint of initial diagnosis and 100 of them with a long-term course of the disease were included. Based on a semi-structured interview, we evaluated the occurrence of headache over the last 4 weeks as well as case history, clinical–neurological investigation and questionnaires about depression, fatigue, and quality of life. Prevalence of headache in all patients was 67%. Patients at the timepoint of symptom manifestation of MS showed the highest prevalence of headache that was ever been recorded of 78%. In general, patients with headache were younger, had a shorter duration of the disease, and were less physically affected. We noticed frequent occurrence of migraine and migraine-like headache. In the course of the disease, patients without disease-modifying drug (DMD) complained more frequently headaches than patients with any kind of therapy. Headache is an important early symptom of MS. This could be shown especially among 78% of patients with clinically isolated syndrome (CIS). Therefore, young people with frequent headache should undergo MRI of the head and in the case of abnormal findings a consecutive detailed differential diagnosis. This could reduce the latency until final diagnosis of MS, which is in general much too long. That way these patients could get the earliest possible treatment, which is important to stop the progression of the disease.

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Abbreviations

CGRP:

Calcitonin gene-related peptide

CNS:

Central nervous system

CIS:

Clinically isolated syndrome

DMD:

Disease-modifying drug

EDSS:

Expanded Disability Status Scale

GCS:

Glucocorticosteroid

ICHD-III:

International Classification of Headache Disorders, 3rd Version

MRI:

Magnetic resonance imaging

MS:

Multiple sclerosis

NMOSD:

Neuromyelitis optica spectrum disorder

PPMS:

Primary progressive MS

RIS:

Radiologically isolated syndrome

RRMS:

Relapsing–remitting MS

Rokoko:

Rostock Headache Questionnaire

SPMS:

Secondary progressive multiple sclerosis

TTH:

Tension-type headache

References

  • Absinta M, Rocca MA, Colombo B, Copetti M, De Feo D, Falini A, Comi G, Filippi M (2012) Patients with migraine do not have MRI-visible cortical lesions. J Neurol 259:2695–2698

    Article  PubMed  Google Scholar 

  • Achiron A, Givon U, Magalashvili D, Dolev M, Liraz Zaltman S, Kalron A, Stern Y, Mazor Z, Ladkani D, Barak Y (2015) Effect of Alfacalcidol on multiple sclerosis-related fatigue: a randomized, double-blind placebo-controlled study. Mult Scler 21(6):767–775

    Article  CAS  PubMed  Google Scholar 

  • Alcaide-Leon P, Cybulsky K, Sankar S, Casserly C, Leung G, Hohol M, Selchen D, Montalban X, Bharatha A, Oh J (2018) Quantitative spinal cord MRI in radiologically isolated syndrome. Neurol Neuroimmunol Neuroinflamm 5(2):e436

    Article  PubMed  PubMed Central  Google Scholar 

  • Asseyer S, Schmidt F, Chien C, Scheel M, Ruprecht K, Bellmann-Strobl J, Brandt AU, Paul F (2018) Pain in AQP4-IgG-positive and MOG-IgG-positive neuromyelitis optica spectrum disorders. Mult Scler J Exp Transl Clin 4(3):2055217318796684

    PubMed  PubMed Central  Google Scholar 

  • Azevedo CJ, Overton E, Khadka S, Buckley J, Liu S, Sampat M, Kantarci O, Lebrun Frenay C, Siva A, Okuda DT, Pelletier D (2015) Early CNS neurodegeneration in radiologically isolated syndrome. Neurol Neuroimmunol Neuroinflamm 2(3):e102

    Article  PubMed  PubMed Central  Google Scholar 

  • Beck AT, Steer RA, Ball R, Ranieri W (1996) Comparison of Beck Depression Inventories-IA and -II in psychiatric outpatients. J Personal Assess 67:588–597

    Article  CAS  Google Scholar 

  • Bermel RA, Weinstock-Guttman B, Bourdette D, Foulds P, You X, Rudick RA (2010) Intramuscular interferon beta-1a therapy in patients with relapsing–remitting multiple sclerosis: a 15-year follow-up study. Mult Scler 16(5):588–596

    Article  CAS  PubMed  Google Scholar 

  • Bevan CJ, Cree BA (2014) Disease activity free status—a new endpoint for a new era in multiple sclerosis. JAMA Neurol 71(3):269–270

    Article  PubMed  Google Scholar 

  • Boneschi FM, Colombo B, Annovazzi P, Martinelli V, Bernasconi L, Solaro C, Comi G (2008) Lifetime and actual prevalence of pain and headache in multiple sclerosis. Mult Scler 14:514–521

    Article  Google Scholar 

  • Bracci-Laudiero L, Aloe L, Buanne P, Finn A, Stenfors C, Vigneti E, Theodorsson E, Lundeberg T (2002) NGF modulates CGRP synthesis in human B-lymphocytes: a possible anti-inflammatory action of NGF? J Neuroimmunol 123(1–2):58–65

    Article  CAS  PubMed  Google Scholar 

  • Chavarro VS, Mealy MA, Simpson A, Lacheta A, Pache F, Ruprecht K, Gold SM, Paul F, Brandt AU, Levy M (2016) Insufficient treatment of severe depression in neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm 3(6):e286

    Article  PubMed  PubMed Central  Google Scholar 

  • Cohen BA, Rivera VM (2010) PRISMS: the story of a pivotal clinical trial series in multiple sclerosis. Curr Med Res Opin 26(4):827–838

    Article  PubMed  Google Scholar 

  • Comi G, Leocani L, Rossi P, Colombo B (2001) Physiopathology and treatment of fatigue in multiple sclerosis. J Neurol 248(3):174–179

    Article  CAS  PubMed  Google Scholar 

  • Comi G, Martinelli V, Rodegher M, Moiola L, Bajenaru O, Carra A, Elovaara I, Fazekas F, Hartung HP, Hillert J, King J, Komoly S, Lubetzki C, Montalban X, Myhr KM, Ravnborg M, Rieckmann P, Wynn D, Young C, Filippi M (2009) Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (precise study): a randomised, double-blind, placebo-controlled trial. Lancet 374:1503–1511

    Article  CAS  PubMed  Google Scholar 

  • D’Amico D, La Mantia L, Rigamonti A, Usai S, Mascoli N, Milanese C, Bussone G (2004) Prevalence of primary headaches in people with multiple sclerosis. Cephalalgia 24:980–984

    Article  PubMed  Google Scholar 

  • De Stefano N, Stromillo ML, Rossi F, Battaglini M, Giorgio A, Portaccio E, Hakiki B, Malentacchi G, Gasperini C, Santangelo M, Bartolozzi ML, Sormani MP, Federico A, Amato MP (2011) Improving the characterization of radiologically isolated syndrome suggestive of multiple sclerosis. PLoS One. https://doi.org/10.1371/journal.pone.0019452

    Article  PubMed  PubMed Central  Google Scholar 

  • De Stefano N, Giorgio A, Tintoré M, Pia Amato M, Kappos L, Palace J, Yousry T, Rocca MA, Ciccarelli O, Enzinger C, Frederiksen J, Filippi M, Vrenken H, Rovira À, MAGNIMS study group (2018) Radiologically isolated syndrome or subclinical multiple sclerosis: MAGNIMS consensus recommendations. Mult Scler 24(2):214–221

    Article  PubMed  Google Scholar 

  • Ergün U, Özer G, Sekercan S, Artan E, Kudiaki C, Ücler S, Coskun Ö, Inan L (2009) Headache in the different phases of relapsing-remitting multiple sclerosis. Neurologist 15:212–216

    Article  PubMed  Google Scholar 

  • Fiesseler FW, Shih R, Szucs P, Silverman ME, Eskin B, Clement M, Saxena R, Allegra J, Riggs RL, Majlesi N (2011) Steroids for migraine headaches: a randomized double-blind, two-armed, placebo-controlled trial. J Emerg Med 40(4):463–468

    Article  PubMed  Google Scholar 

  • Flachenecker P, Zettl U, Götze U, Haas J, Schimrigk S, Elias W, Pette M, Eulitz M, Hennig M, Bertram J, Hollweck R, Neiss A, Daumer M, Pitschnau-Michel D, Rieckmann P (2005) MS registry in Germany—design and first results of the pilot phase. Nervenarzt 76(8):967–975

    Article  CAS  PubMed  Google Scholar 

  • Flachenecker P, Stuke K, Elias W, Freidel M, Haas J, Pitschnau-Michel D, Schimrigk S, Zettl U, Rieckmann P (2008) Multiple sclerosis registry in Germany: results of the extension phase 2005/2006. Dtsch Ärztebl 105(7):113–119

    Google Scholar 

  • Flachenecker P, Kobelt G, Berg J, Capsa D, Gannedahl M, European Multiple Sclerosis Platform (2017) New insights into burden and costs of multiple sclerosis in Europe: results of Germany. Mult Scler 23(2_suppl):78–90. https://doi.org/10.1177/1362458517708141

    Article  PubMed  Google Scholar 

  • Fox EJ, Rhoades RW (2012) New treatments and treatment goals for patients with relapsing-remitting multiple sclerosis. Curr Opin Neurol Supplz. https://doi.org/10.1097/01.wco.0000413320.94715.e9

    Article  Google Scholar 

  • Geraldes R, Ciccarelli O, Barkhof F, De Stefano N, Enzinger C, Filippi M, Hofer M, Paul F, Preziosa P, Rovira A, DeLuca GC, Kappos L, Yousry T, Fazekas F, Frederiksen J, Gasperini C, Sastre-Garriga J, Evangelou N, Palace J, MAGNIMS study group (2018) The current role of MRI in differentiating multiple sclerosis from its imaging mimics. Nat Rev Neurol 14(4):199–213

    Article  PubMed  Google Scholar 

  • Granberg T, Martola J, Kristoffersen-Wiberg M, Aspelin P, Fredrikson S (2013) Radiologically isolated syndrome–incidental magnetic resonance imaging findings suggestive of multiple sclerosis, a systematic review. Mult Scl 19(3):271–280

    Article  Google Scholar 

  • Headache Classification Committee of the International Headache Society (2013) The international classification of headache disorders, 3rd edition. Cephalalgia 33: 629–808

    Article  Google Scholar 

  • Howell O, Reeves C, Nicholas R, Carassiti D, Radotra B, Gentleman S, Serafini B, Aloisi F, Roncaroli F, Magliozzi R, Reynolds R (2011) Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain 134:2755–2771

    Article  PubMed  Google Scholar 

  • Jarius S, Ruprecht K, Kleiter I, Borisow N, Asgari N, Pitarokoili K, Pache F, Stich O, Beume LA, 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, in cooperation with the Neuromyelitis Optica Study Group (NEMOS) (2016) MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J Neuroinflamm 13(1):280

    Article  CAS  Google Scholar 

  • Kantarci OH, Lebrun C, Siva A, Keegan MB, Azevedo CJ, Inglese M, Tintoré M, Newton BD, Durand-Dubief F, Amato MP, De Stefano N, Sormani MP, Pelletier D, Okuda DT (2016) Primary progressive multiple sclerosis evolving from radiologically isolated syndrome. Ann Neurol 79(2):288–294

    Article  PubMed  Google Scholar 

  • Kappos L, Polman CH, Freedman MS, Edan G, Hartung HP, Miller DH, Montalban X, Barkhof F, Bauer L, Jakobs P, Pohl C, Sandbrink R (2006) Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 67(7):1242–1249

    Article  CAS  PubMed  Google Scholar 

  • Kister I, Caminero AB, Monteith TS, Soliman A, Bacon TE, Bacon JH, Kalina JT, Inglese M, Herbert J, Lipton RB (2010) Migraine is comorbid with multiple sclerosis and associated with a more symptomatic MS course. J Headache Pain 11.5:417–425

    Article  Google Scholar 

  • Klein M, Woehrl B, Zeller G, Straube A (2013) Stabbing headache as a sign of relapses in multiple sclerosis. Headache 53:1159–1161

    Article  PubMed  Google Scholar 

  • Kobelt G, Berg J, Lindgren P, Jönsson B (2006) Costs and quality of life of patients with multiple sclerosis in Europe. J Neurol Neurosurg Psychiatry 77(8):918–926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kovacs K, Bors L, Tothfalusi L, Jelencsik I, Bozsik G, Kerenyi L, Komoly S (1989) Cerebrospinal fluid (CSF) investigations in migraine. Cephalalgia 9(1):53–57

    Article  CAS  PubMed  Google Scholar 

  • Kowalec K, McKay KA, Patten SB, Fisk JD, Evans C, Tremlett H, Marrie RA, CIHR Team in Epidemiology and Impact of Comorbidity on Multiple Sclerosis (ECoMS) (2017) Comorbidity increases the risk of relapse in multiple sclerosis: a prospective study. Neurology 89(24):2455–2461

    Article  PubMed  PubMed Central  Google Scholar 

  • Kropp P, Müller B, Barchmann D, Angeli A, Straube A (2011) Does multiple sclerosis facilitate migraine. Fortschr Neurol Psychiatr 79(8):467–469

    Article  CAS  PubMed  Google Scholar 

  • Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33.11:1444–1452

    Article  Google Scholar 

  • Lebrun C (2015) The radiologically isolated syndrome. Rev Neurol (Paris) 171(10):698–706

    Article  CAS  Google Scholar 

  • Levy D (2009) Migraine pain, meningeal inflammation, and mast cells. Curr Pain Headache Rep 13(3):237–240

    Article  PubMed  Google Scholar 

  • Magliozzi R, Howell O, Vora A, Serafini B, Nicholas R, Puopolo M, Reynolds R, Aloisi F (2007) Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain 130(4):1089–1104

    Article  PubMed  Google Scholar 

  • Magliozzi R, Howell O, Reeves C, Roncaroli F, Nicholas R, Serafini B, Aloisi F, Reynolds R (2010) A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol 68(4):477–493

    Article  CAS  PubMed  Google Scholar 

  • Makhani N, Lebrun C, Siva A, Brassat D, Carra Dallière C, de Seze J, Du W, Durand Dubief F, Kantarci O, Langille M, Narula S, Pelletier J, Rojas JI, Shapiro ED, Stone RT, Tintoré M, Uygunoglu U, Vermersch P, Wassmer E, Okuda DT, Pelletier D (2017) Radiologically isolated syndrome in children: clinical and radiologic outcomes. Neurol Neuroimmunol Neuroinflamm 4(6):e395

    Article  PubMed  PubMed Central  Google Scholar 

  • Marrie RA (2017) Comorbidity in multiple sclerosis: implications for patient care. Nat Rev Neurol 13(6):375–382

    Article  PubMed  Google Scholar 

  • Masters-Israilov A, Robbins MS (2017) Headache in neuromyelitis optica. Curr Pain Headache Rep 21(4):20

    Article  PubMed  Google Scholar 

  • Melo-Carrillo A, Strassmann AM, Nir RR, Schain A, Noseda R, Stratton J, Burstein R (2017) Fremanezumab—a humanized monoclonal anti-CGRP antibody—inhibits thinly myelinated (Aδ) but not unmyelinated (C) meningeal nociceptors. J Neurosci. 37(44):10587–10596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller DH, Leary SM (2009) Treatment of clinically isolated syndrome: to be PreCISe. Lancet 374:1475–1476

    Article  PubMed  Google Scholar 

  • Mizuno Y, Shinoda K, Watanabe M, Matsushita T, Yamasaki R, Kira JI (2018) Short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms in NMOSD. Neurol Neuroimmunol Neuroinflamm 5(3):e447

    Article  PubMed  PubMed Central  Google Scholar 

  • Möhrke J, Kropp P, Zettl UK (2013) Headaches in multiple sclerosis patients might imply an inflammatorial process. PLoS One. https://doi.org/10.1371/journal.pone.0069570

    Article  PubMed  PubMed Central  Google Scholar 

  • Moisset X, Ouchchane L, Guy N, Bayle DJ, Dallel R (2013) Migraine headaches and pain with neuropathic characteristics: comorbid conditions in patients with multiple sclerosis. Pain 154:2691–2699

    Article  PubMed  Google Scholar 

  • Moreno MA, Or-Geva N, Aftab BT, Khanna R, Croze E, Steinman L, Han MH (2018) Molecular signature of Epstein-Barr virus infection in MS brain lesions. Neurol Neuroimmunol Neuroinflamm 5(4):e466

    Article  PubMed  PubMed Central  Google Scholar 

  • Müller B, Baum A, Holzhausen M, Grittner U, Hilgendorf I, Martus P, Altiner A, Evers S, Rolfs A, Zettl UK, Kropp P (2014) The Rostock Headache Questionnaire (“Rokoko”)—validation of a tool to screen and to qualify primary headaches. Fortschr Neurol Psychiatr 82(3):145–148

    Article  PubMed  Google Scholar 

  • Nicoletti A, Patti F, Lo Fermo S, Liberto A, Castiglione A, Laisa P, Garifoli A, La Naia F, Maimone D, Sorbello V, Contrafatto D, Zappia M (2008) Headache and multiple sclerosis: a population-based case–control study in Catania, Sicily. Cephalalgia 28:1163–1169

    Article  CAS  PubMed  Google Scholar 

  • Patejdl R, Zettl UK (2017) Spasticity in multiple sclerosis: Contribution of inflammation, autoimmune mediated neuronal damage and therapeutic interventions. Autoimmun Rev 16(9):925–936

    Article  CAS  PubMed  Google Scholar 

  • Penner IK, Paul F (2017) Fatigue as a symptom or comorbidity of neurological diseases. Nat Rev Neurol. (11):662–675

  • Penner IK, Raselli C, Stöcklin M, Opwis K, Kappos L (2007) The FSMC (Fatigue Scale for Motor and Cognitive Functions)—a new instrument to assess MS-related fatigue. Mult Scler 13:238

    Article  Google Scholar 

  • Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O’Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69(2):292–302

    Article  PubMed  PubMed Central  Google Scholar 

  • Putzki N, Pfriem A, Limmroth V, Yaldizli O, Tettenborn B, Diener HC, Katsarava Z (2009) Prevalence of migraine, tension-type headache and trigeminal neuralgia in multiple sclerosis. Eur J Neurol 16:262–267

    Article  CAS  PubMed  Google Scholar 

  • Reder AT, Ebers GC, Traboulsee A, Li D, Langdon D, Goodin DS, Bogumil T, Beckmann K, Konieczny A, Investigators of the 16-Year Long-Term Follow-Up Study (2010) Cross-sectional study assessing long-term safety of interferon-beta-1b for relapsing-remitting MS. Neurology 74(23):1877–1885

    Article  CAS  PubMed  Google Scholar 

  • Reich DS, Lucchinetti CF, Calabresi PA (2018) Multiple sclerosis. N Engl J Med 378(2):169–180. https://doi.org/10.1056/NEJMra1401483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rovaris M, Bozzali M, Rocca MA, Colombo B, Filippi M (2001) An MR study of tissue damage in the cervical cord of patients with migraine. J Neurol Sci 183(1):43–46

    Article  CAS  PubMed  Google Scholar 

  • Russell FA, King R, Smillie SJ, Kodji X, Brain SD (2014) Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev 94(4):1099–1142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Skierlo S, Rommer PS, Zettl UK (2016) Symptomatic treatment in multiple sclerosis-interim analysis of a nationwide registry. Acta Neurol Scand. https://doi.org/10.1111/ane.12612

    Article  PubMed  Google Scholar 

  • Solomon AJ, Schindler MK, Howard DB, Watts R, Sati P, Nickerson JP, Reich DS (2015) “Central vessel sign” on 3T FLAIR* MRI for the differentiation of multiple sclerosis from migraine. Ann Clin Transl Neurol 3(2):82–87

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Solomon AJ, Bourdette DN, Cross AH, Applebee A, Skidd PM, Howard DB, Spain RI, Cameron MH, Kim E, Mass MK, Yadav V, Whitham RH, Longbrake EE, Naismith RT, Wu GF, Parks BJ, Wingerchuk DM, Rabin BL, Toledano M, Tobin WO, Kantarci OH, Carter JL, Keegan BM, Weinshenker BG (2016) The contemporary spectrum of multiple sclerosis misdiagnosis: a multicenter study. Neurology 87(13):1393–1399

    Article  PubMed  PubMed Central  Google Scholar 

  • Straube A, Aicher B, Förderreuther S, Eggert T, Köppel J, Möller S, Schneider R, Haag G (2013) Period prevalence of self-reported headache in the general population in Germany from 1995 to 2005 and 2009: results from annual nationwide population-based cross-sectional surveys. J Headache Pain 14:14:11. https://doi.org/10.1186/1129-2377-14-11

    Article  PubMed  PubMed Central  Google Scholar 

  • Thompson AJ, Baranzini SE, Geurts J, Hemmer B, Ciccarelli O (2018) Multiple Sclerosis. Lancet 391(10130):1622–1636

    Article  PubMed  Google Scholar 

  • Vacca G, Marano E, Brescia Morra V, Lanzillo R, De Vito M, Parente E, Orefice G (2007) Multiple sclerosis and headache co-morbidity. A case–control study. Neurol Sci 28:133–135

    Article  CAS  PubMed  Google Scholar 

  • Veauthier C, Paul F (2014) Sleep disorders in multiple sclerosis and their relationship to fatigue. Sleep Med. 2014 (1):5–14

  • Villani V, Prosperini L, Ciuffoli A, Pizzolato R, Salvetti M, Pozzilli C, Sette G (2008) Primary headache and multiple sclerosis: preliminary results of a prospective study. Neurol Sci 29:S146–S148

    Article  PubMed  Google Scholar 

  • Ware JE, Kosinski M, Keller SD (1996) A 12-item Short Form Health Survey: construction of scales and preliminary test of reliability and validity. Med care 34:220–233

    Article  PubMed  Google Scholar 

  • Wingerchuk DM, Banwell B, Bennett JL et al (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85:177–189

    Article  PubMed  PubMed Central  Google Scholar 

  • Zettl UK, Lehmitz R, Mix E (2009) Klinische Liquordiagnostik, 2 Auflage. Walter de Gruyter, Berlin, p 233

    Google Scholar 

  • Zettl UK, Stüve O, Patejdl R (2012) Immune-mediated CNS diseases: a review on nosological classification and clinical features. Autoimmun Rev 11(3):167–173

    Article  PubMed  Google Scholar 

  • Zeydan B, Gu X, Atkinson EJ, Keegan BM, Weinshenker BG, Tillema JM, Pelletier D, Azevedo CJ, Lebrun-Frenay C, Siva A, Okuda DT, Kantarci K, Kantarci OH (2018) Cervical spinal cord atrophy: an early marker of progressive MS onset. Neurol Neuroimmunol Neuroinflamm 5(2):e435

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Klinik für Neurologie, Krankenhaus Martha-Maria Halle-Dölau, Röntgenstraße 1, 06120, Halle, Germany

    Marcel Gebhardt & Frank Hoffmann

  2. Institute of Medical Psychology and Medical Sociology, Medical Faculty, University of Rostock, Gehlsheimer Straße 20, 18147, Rostock, Germany

    Peter Kropp

  3. Neuroimmunological Section, Department of Neurology, University of Rostock, Rostock, Germany

    Uwe K. Zettl

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  1. Marcel Gebhardt
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  2. Peter Kropp
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  3. Frank Hoffmann
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  4. Uwe K. Zettl
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Correspondence to Marcel Gebhardt.

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The study was approved by the ethics committee of the Medical Association Saxony-Anhalt (no. 7/15). All participants got pertinent information and gave their permission to be part of a study. All participants gave informed and written consent.

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The data sets used and analysed during the current study available from the corresponding author on reasonable request.

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Gebhardt, M., Kropp, P., Hoffmann, F. et al. Headache in the course of multiple sclerosis: a prospective study. J Neural Transm 126, 131–139 (2019). https://doi.org/10.1007/s00702-018-1959-0

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