Background/Purpose:

Headache, especially migraine, is frequent and one of the most common neuropsychiatric manifestations in systemic lupus erythematosus (SLE). A possible mechanism for this is that the threshold for migraine activation could be lower in SLE patients due to immunological, biochemical or structural disturbances or changes. Glutamatergic neurotransmission, involving the NMDA-receptor is considered important in migraine pathophysiology, and antibodies (ab) against the NR2 subtype of the NMDA receptor (anti-NR2 ab) are found in SLE patients. Ab against ribosomal P proteins (anti-P ab) are potentially neuropathogenic and associated with diffuse and complex neuropsychiatric manifestations in SLE. Protein S100B, a biomarker of astro-glial cell activation, is linked to neuropsychiatric SLE in some studies. We investigated whether structural abnormalities of the brain as revealed by MRI volumetry, or anti-NR2 ab, anti-P ab or increased protein S100B in cerebrospinal fluid (CSF) were associated with primary headaches in SLE.

Methods:

Sixty-seven SLE patients, all fulfilling the ACR criteria, and 67 age- and gender matched healthy subjects, participated in the study. Headache was assessed through a structured interview and classified according to the International Classification of Headache Disorders. Anti-NR2 ab, anti-P ab and protein S100B were measured in CSF. Global volumes of grey matter (GM) and white matter (WM) were estimated from cerebral MRI images by applying the SPM8 software. 

Results:

SLE patients in this cohort had, in accordance with other studies, more migraine than age- and gender matched healthy subjects (36% vs 19%, P = 0.03). In logistic regression analyses, higher GM volumes in the SLE patients reduced the odds for headache in general (OR 0.98, P = 0.05) and for migraine in particular (OR 0.95, P = 0.004). This was not evident for pure tension type headache. Higher WM volumes in the patients increased the odds for migraine (OR 1.04, P = 0.007). In contrast, no associations were found between headache and brain volumes in the healthy subjects. No associations were revealed between headache or headache categories and anti-NR2 ab, anti-P ab or S100B in the SLE patients.

Descriptive data in the SLE patients

Data are given as median and range; GM, grey matter; volumes are given in cm³; * measured in CSF; anti-NR2 ab, values are given as a ratio against an internal calibrator with defined signal intensity; anti-P ab in ug/mL; S100B in pg/mL  

Conclusion:

SLE patients with reduced GM volumes have higher probability for migraine and headache in general. However, no associations between headache or headache categories and anti-NR2 ab, anti-P ab or protein S100B were found. These results indicate that unknown disease processes in SLE resulting in GM loss may increase headache and migraine susceptibility.