Headache Prevalence and Phenotype in Myelin Oligodendrocyte Glycoprotein Antibody -Associated Disease (MOGAD)

Official title

Single-center Ambispective Observational Study to Evaluate the Prevalence and Phenotype of Headache in Patients With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGHEAD).

Overview

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) is an inflammatory demyelinating disorder of the central nervous system characterized by antibodies targeting myelin oligodendrocyte glycoprotein (MOG). Although the disease most commonly presents with optic neuritis, myelitis, or acute disseminated encephalomyelitis, headache has increasingly been reported as a potentially relevant and disabling symptom. However, the prevalence and clinical characteristics of headache in MOGAD remain poorly defined. The purpose of this monocentric ambispective observational study is to evaluate the prevalence and clinical phenotype of headache in adult patients with MOGAD. The study aims to answer the following research questions: How common is headache in patients with MOGAD, what are its clinical characteristics, and does it show any correlation with any specific disease features? The primary objective is to estimate the prevalence of acute and/or chronic headache in patients with MOGAD. Secondary objectives include describing headache characteristics (location, duration, intensity, associated symptoms, and response to treatment), assessing the presence and evolution of pre-existing primary headache disorders, and exploring potential associations between headache and laboratory or neuroradiological findings, including anti-MOG antibody titers, cerebrospinal fluid (CSF) oligoclonal bands, and the location of inflammatory or demyelinating lesions on MRI. Approximately 25 adult patients with MOGAD followed at the Multiple Sclerosis Center and Headache Clinic of the Fondazione Policlinico A. Gemelli IRCCS will be included. Clinical, laboratory, and neuroradiological data will be collected retrospectively and prospectively from medical records.

Detailed description

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) is an inflammatory demyelinating disorder of the central nervous system associated with antibodies directed against myelin oligodendrocyte glycoprotein (MOG). The clinical spectrum of the disease includes optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, and less frequently cortical encephalitis or brainstem and cerebellar syndromes. While pain has increasingly been recognized as an important component of the disease burden, the clinical relevance of headache in this population has not been systematically characterized.

Headache may occur during acute inflammatory attacks or persist during the chronic phase of the disease. Different clinical presentations have been described, including migraine-like, orbital, and cervicogenic-like headaches. Moreover, some patients may have a history of primary headache disorders hat precede the onset of MOGAD. The relationship between headache and disease-specific biological or radiological features remains unclear. In particular, it is not yet established whether headache may represent an early manifestation of the disease, a symptom associated with inflammatory activity, or a clinical feature related to specific anatomical sites of central nervous system involvement.

This study is a monocentric ambispective observational study conducted at the Multiple Sclerosis Center and the Headache Clinic of Fondazione Policlinico A. Gemelli IRCCS. The study will include approximately 25 adult patients diagnosed with MOGAD according to the International MOGAD Panel proposed diagnostic criteria. Both retrospective and prospective data will be analyzed.

Clinical, laboratory, and neuroradiological information will be collected from medical records generated during routine clinical care. Data will be extracted from both paper and electronic medical charts and recorded in a password-protected database. Demographic variables will include age, sex, ethnicity, body mass index, and smoking status. Clinical variables will include comorbid autoimmune diseases, non-neurological comorbidities, age at disease onset, clinical presentation at onset (for example optic neuritis, acute disseminated encephalomyelitis, encephalitis, or myelitis), and disease course (monophasic or relapsing).

Detailed information regarding headache will be collected, including age at headache onset, temporal relationship with MOGAD diagnosis, headache phenotype, localization, duration, frequency, intensity, associated symptoms, and response to treatments. The presence of primary headache prior to the onset of MOGAD and its clinical evolution after the diagnosis will also be assessed.

Laboratory data will include anti-MOG antibody status and cerebrospinal fluid findings, particularly the presence or absence of oligoclonal bands. Neuroradiological variables will include magnetic resonance imaging findings of the brain and spinal cord, with particular attention to the anatomical location of inflammatory or demyelinating lesions.

The study will also explore potential associations between headache characteristics and disease-related factors, including laboratory biomarkers and neuroradiological features, in order to better define the clinical relevance of headache within the spectrum of MOGAD. The planned enrollment period is 12 months, with an overall study duration of 24 months.

Primary outcome measures

• Prevalence of headache in patients with yelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) [Time frame: From March, 31 2026 to December, 30 2026]
• Clinical characteristics of headache in patients with MOGAD [Time frame: From 31 march to 30 december 2026]

Secondary outcome measures (1)

• Correlation between headache and laboratory and neuroimaging findings in MOGAD [Time frame: From March, 31 2026 to December, 30 2026]

Eligibility criteria

Inclusion criteria

• Patients older than 18 years with a diagnosis of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) according to the International MOGAD Panel proposed criteria
• Ability to understand and provide written informed consent for the prospective cohort.

Exclusion criteria

• Individuals under 18 years of age
• Inability to provide informed consent for the prospective cohort

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Straube A, Andreou A. Primary headaches during lifespan. J Headache Pain. 2019 Apr 8;20(1):35. doi: 10.1186/s10194-019-0985-0. PMID 30961531
• Asseyer S, Hamblin J, Messina S, Mariano R, Siebert N, Everett R, Kuker W, Bellmann-Strobl J, Ruprecht K, Jarius S, Leite MI, U Brandt A, Paul F, Palace J. Prodromal headache in MOG-antibody positive optic neuritis. Mult Scler Relat Disord. 2020 May;40:101965. doi: 10.1016/j.msard.2020.101965. Epub 2020 Jan 25. PMID 32062443
• Asseyer S, Cooper G, Paul F. Pain in NMOSD and MOGAD: A Systematic Literature Review of Pathophysiology, Symptoms, and Current Treatment Strategies. Front Neurol. 2020 Aug 21;11:778. doi: 10.3389/fneur.2020.00778. eCollection 2020. PMID 33473247
• Diaz P, Nealon NE, Kaunzner UW. Pain and Headache in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease. Curr Pain Headache Rep. 2025 Jan 29;29(1):39. doi: 10.1007/s11916-024-01322-7. PMID 39878785
• Marignier R, Hacohen Y, Cobo-Calvo A, Probstel AK, Aktas O, Alexopoulos H, Amato MP, Asgari N, Banwell B, Bennett J, Brilot F, Capobianco M, Chitnis T, Ciccarelli O, Deiva K, De Seze J, Fujihara K, Jacob A, Kim HJ, Kleiter I, Lassmann H, Leite MI, Linington C, Meinl E, Palace J, Paul F, Petzold A, Pittock S, Reindl M, Sato DK, Selmaj K, Siva A, Stankoff B, Tintore M, Traboulsee A, Waters P, Wauban PMID 34418402
• Banwell B, Bennett JL, Marignier R, Kim HJ, Brilot F, Flanagan EP, Ramanathan S, Waters P, Tenembaum S, Graves JS, Chitnis T, Brandt AU, Hemingway C, Neuteboom R, Pandit L, Reindl M, Saiz A, Sato DK, Rostasy K, Paul F, Pittock SJ, Fujihara K, Palace J. Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria. Lancet Neurol. 2023 Mar; PMID 36706773
• Hor JY, Fujihara K. Epidemiology of myelin oligodendrocyte glycoprotein antibody-associated disease: a review of prevalence and incidence worldwide. Front Neurol. 2023 Sep 15;14:1260358. doi: 10.3389/fneur.2023.1260358. eCollection 2023. PMID 37789888
• Flanagan EP. Neuromyelitis Optica Spectrum Disorder and Other Non-Multiple Sclerosis Central Nervous System Inflammatory Diseases. Continuum (Minneap Minn). 2019 Jun;25(3):815-844. doi: 10.1212/CON.0000000000000742. PMID 31162318

Identifiers

NCT: NCT07479212 · 27123

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗