Abstract

Objective

This study aims to increase awareness and improve the management of migraines associated with antiphospholipid syndrome (APS) and antiphospholipid (aPL) antibody positivity, particularly in patients with non-revealing imaging studies. This condition remains under-recognized even among neurologists and headache specialists.

Background

Neurological symptoms, including refractory headaches, can be a manifestation of APS or aPL positivity. Despite normal or inconclusive imaging findings, some patients experience migraine-like headaches that are resistant to conventional treatments but show significant improvement with anticoagulation. However, this unique disease mechanism remains poorly understood and is often overlooked, even by neurologists and headache specialists. We present a case of a young woman with an intense, new-onset migraine-like headache, unresponsive to standard therapies yet successfully treated with anticoagulation.

Methods

A 22-year-old woman with a history of joint pain, myalgia, dysuria, and fatigue presented with new-onset, migraine-like headaches with aura. She had no prior thrombotic events, neurological disorders, or neuropsychiatric symptoms and had never been pregnant. Her family history was notable for systemic lupus erythematosus.

Neurological examination revealed absent deep tendon reflexes in the upper extremities, decreased pinprick sensation in the left face and arm, and a rash on her hands resembling livedo reticularis. Brain MRI, MRA, and MRV were performed to evaluate secondary causes of headaches but were inconclusive. Despite the absence of apparent radiologic abnormalities, autoimmune and infectious disease workups revealed elevated anticardiolipin IgM antibody titers (21 MPL), suggesting aPL positivity.

Initial treatment with indomethacin and a steroid taper failed to relieve symptoms. However, a trial of low-molecular-weight heparin (Lovenox) led to the complete resolution of her headaches. She was subsequently transitioned to long-term anticoagulation with warfarin, with sustained symptom relief.

Conclusions

The pathophysiological basis for the dramatic response of migraine-like headaches to anticoagulation in APS/aPL-positive patients remains unclear. Importantly, even in cases where imaging studies do not reveal significant abnormalities, anticoagulant therapy may still provide substantial clinical benefit. However, the optimal duration of anticoagulation therapy in these patients is unknown, necessitating individualized treatment decisions and close follow-up. Notably, this phenomenon remains largely unrecognized, even among neurologists and headache specialists, leading to potential delays in diagnosis and treatment. Untreated migraines in APS/aPL patients can worsen, potentially mimicking transient ischemic attacks or strokes. Given the significant impact of migraines on quality of life, healthcare providers should consider APS/aPL evaluation in patients with refractory headaches and explore anticoagulation as a therapeutic option when appropriate. Further research is warranted to define better anticoagulation therapy's role, duration, and mechanisms in this patient population.