Patterns of headache in patients with antiphospholipid syndrome in relation to autoantibodies

The interplay between Antiphospholipid syndrome (APS) and migraine is very controversial; migraine is believed to be the most common neurologic symptom in APS, and there are claims that migraineurs have abnormally high Antiphospholipid antibodies (aPL), yet the reports differ widely. Nevertheless, APS could lead to various other types of headaches; both primary and secondary, leaving patients susceptible to exacerbation of symptoms, overlapping of headaches, and atypical presentations.

To describe types and characteristics of headache in a cohort of patients with antiphospholipid syndrome (APS) in comparison to healthy controls. And investigate their possible relation with antiphospholipid antibodies (aPL) and MRI brain findings in patients with APS.

We recruited 76 patients with APS consecutively, between February 2024 and August 2025. From Ain shams university hospital; neurology, internal medicine, and obstetric and gynecology departments, along with 60 matched controls. Patients and controls underwent neurological examination and were evaluated for headache according to the International Headache Society criteria (IHS), Impact and severity were assessed by Migraine Disability Assessment (MIDAS) and Headache Impact Test (HIT). All participants had a brain MRI.

A total of 76 patients; 70 females and 6 males, mean age for patients at presentation was 35 ± 8.73 years; mean disease duration was 5 ± 3 years; mean Body mass index (BMI) was 22.38 ± 1.46. Headache was reported by 87% of patients; of which 16 patients suffered secondary type headaches (21%); and 50 patients had primary headaches (65.7%); with migraine being the most common (35%). Anticardiolipin (ACL) antibodies were the most common aPL detected (76.4%) in APS patients. MRI brain was normal in 86% of APS patients with primary headaches, Meanwhile, APS patients with triple positive antibodies showed significantly more abnormal MRI findings (p = 0.04). Headache severity was significantly more in APS patients (p = 0.04) Factors affecting headache severity were APS disease duration, BMI, triple aPL positivity (p = 0.03, 0.00, 0.02 respectively).

Primary and secondary types of headaches are frequently reported in Patients with APS, primary headache being more common; migraine in particular. APS patients had significantly more severe headaches. MRI brain was normal in the majority of APS patients with primary headaches and healthy controls. Yet, patients with triple positive antibodies showed more abnormal MRI findings. APS disease duration, BMI, triple aPL were independent factors for headache severity.