Journal of Neural Transmission

, Volume 126, Issue 2, pp 131–139 | Cite as

Headache in the course of multiple sclerosis: a prospective study

  • Marcel GebhardtEmail author
  • Peter Kropp
  • Frank Hoffmann
  • Uwe K. Zettl
Neurology and Preclinical Neurological Studies - Original Article


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.


Clinically isolated syndrome Headache Migraine Multiple sclerosis Radiologically isolated syndrome 



Calcitonin gene-related peptide


Central nervous system


Clinically isolated syndrome


Disease-modifying drug


Expanded Disability Status Scale




International Classification of Headache Disorders, 3rd Version


Magnetic resonance imaging


Multiple sclerosis


Neuromyelitis optica spectrum disorder


Primary progressive MS


Radiologically isolated syndrome


Relapsing–remitting MS


Rostock Headache Questionnaire


Secondary progressive multiple sclerosis


Tension-type headache



No funding.

Compliance with ethical standards

Ethical approval

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.

Availability of data and material

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

Conflict of interest

All authors declare that they have no competing interests.


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Klinik für NeurologieKrankenhaus Martha-Maria Halle-DölauHalleGermany
  2. 2.Institute of Medical Psychology and Medical Sociology, Medical FacultyUniversity of RostockRostockGermany
  3. 3.Neuroimmunological Section, Department of NeurologyUniversity of RostockRostockGermany

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