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.

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.

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

Patients attending the Multiple Sclerosis Center and the Headache Clinic at Fondazione Policlinico A. Gemelli IRCCS who are diagnosed with MOGAD