Table 7 Baseline characteristics of published studies investigating headache in systemic lupus erythematosus (SLE) patients: correlations with MRI and immunological investigations (1982–2023)
Study | Population | Headache prevalence | MRI findings | Key conclusions |
|---|---|---|---|---|
1. Isenberg et al. (1982) [11] | 30 SLE, 30 control | -Migraine: 40% vs. 13% control | Not included | No significant differences were found between the patients and controls, who had classical and common migraine or visual auras without headache, with regard to a family History of migraine, the age of onset of the migraine, Raynaud’s phenomenon, or use of oral contraceptives. Increased activity of the lupus was not generally associated with an increase in migraine attacks. |
2. Markus et al. (1992) [12] | 90 SLE, 90 control | -Migraine: 35% vs. 16% control | Not included | Both migraine and non-migrainous headaches were more common in SLE patients and often responded to specific SLE treatment but no association with disease activity or antiphospholipid antibodies. |
3. Sfikakis et al. (1998) [5] | 78 SLE patients, 89 control | -All headache:32% vs. 30% control - TTH most frequent - Migraine: ¼ of headache | Not included | No specific association between headache and clinical, serological features of SLE, including Raynaud’s phenomenon nor the presence of anticardiolipin antibodies. |
4. Fernández-Nebro et al. (1999) [13] | 71 SLE, 71 control | -all headache: 46.5% -Migraine: 23.9% -TTH: 22.5% | Not included | Patients with (SLE) show no significant differences from healthy controls in terms of headache presence and type. Additionally, there are no notable clinical or immunological distinctions among SLE patients with and without tension-type headache or migraine. |
5. Glanz et al. (2001) [14] | 186 SLE patients | -All headache: 62% -Migraine: 39% -Non migraine: 23% | Not included | There were no significant associations between headache type and other clinical, serologic, or treatment features of the disease. |
6. Omdal et al. (2001) [15] | 58 SLE patients | - All headache: 66% - Migraine: 31.9% -TTH: 15.3% | Not included | Headaches were not associated with disease activity or any other disease associated variable, including tests for antiphospholipid antibodies. Migraine and tension-type headaches associated with psychological distress. |
7. Appenzeller & Costallat (2004) [16] | 80 SLE patients, 40 RA patients, 40 controls | -Migraine: 42.5% | Not included | Active migraine was associated with higher disease activity, antiphospholipid antibodies, worsening of Raynaud’s phenomenon and increased cumulative organ damage. |
8. Mitsikostas et al. (2004) [17] | Pooled data from eight studies | -Migraine: 57.1% -TTH: 23.5% | Not included | No strong evidence for the concept of ‘lupus headache,’ and no identified neither pathogenetic mechanism nor an association between headache and the disease status, including CNS involvement. |
9. Whitelaw et al. (2004) [18] | 85 SLE patients, compared to 61 controls | -All headache:48% -Migraine:38% vs. 6%control -TTH: 10% vs. 66%control | Not included | Migrainous headaches more common in lupus patients than in healthy controls but not statistically associated with flares of systemic disease, the ACA syndrome, Raynaud’s phenomenon or increased SLEDAI score |
10. Lessa et al., (2006) [19] | 115 SLE and 92 control | -All headache: 75.7% vs. 66% control - Migraine: 66.1% -TTH:13.9% | Not included | Both headache and migraine were associated with Raynaud’s phenomenon in SLE patients |
11. Bicakci et al. (2008) [20] | 48 SLE patients | -All patients has headache with VAS > or = 4 -Migraine: 39.6% -TTH: 54.1% | Abnormal MRI in 37.5%, mostly as periventricular and subcortical focal lesions | Significant correlation found between abnormal MRI findings with advanced age and prolonged disease duration. |
12. Katsiari et al. (2011) [3] | 72 SLE/control pairs and 48 MS patients | -Migraine: SLE patients (21%), MS patients (23%), and controls (22%) - Chronic TTH:12.5% SLE vs. 1.4% control, 8.3 MS | Not included | No associations of any headache type with particular clinical manifestations, autoantibody, or disease activity, either in SLE or MS patient groups. Migraine should be no longer considered a neurologic manifestation of systemic or organ-specific autoimmunity. Increased migraine prevalence in these patients found in previous studies could be due to methodological weaknesses. |
13. Tjensvoll et al. (2011) [21] | 67 SLE compared with 67 controls | -All headache: 82% vs. 72% control - Migraine: 36% vs. 19% control - TTH: 60% vs. 58% in controls | − 18% infarction vs. 3% in control - SLE patinets had more WMHs than control | Migraine is more prevalent in SLE patients, associated with depression like in the general population, but not associated with disease activity or abnormalities detected on cerebral MRI, in CSF, or any SLE characteristics except from SLE photosensitivity. |
14. Hanly et al. (2013) [22] | 1,732 SLE patients | -All headache: 17.8% at enrollment, increased to 58% after 10 years | Not included | Headache associated with other neuropsychiatric events, but not with specific SLE disease markers. |
15. Hawro et al. (2015) [23] | 57 SLE and 69 control | -All headache: 39% | Not included | Autoantibodies to β2GPI are linked to non-specific headaches, ischemic stroke and seizures, and show a better predictive value than aCL and LA. |
16. Sarbu et al. (2015) [24] | 108 newly diagnosed NPSLE patients | -All headache: 28.5% | Brain abnormalities in 59.3%, including small vessel disease, large vessel disease, and inflammatory-like lesions | Cerebrovascular syndrome correlated with LVD and microbleeds, cognitive dysfunction with WMH and myelopathy with inflammatory-like lesions. Low C4 and CH50 correlated with inflammatory-like lesions and lupus anticoagulant with WMH, microbleeds and atrophy. |
17. Tjensvoll et al. (2016) [25] | 67 SLE, 67 control | -All headache: 82% vs. 72% control -Migraine: 36% vs. 19% control | Larger GM volumes in SLE patients reduced the odds for headache in general and for migraine in particular No localized loss of GM was observed. Larger WM volumes in patients increased the odds for migraine. These findings could not be confirmed in healthy subjects. | SLE patients with migraine have a diffuse reduction in GM compared to patients without migraine. This finding was not observed in healthy subjects with migraine. Neither anti-NR2 and anti-P antibodies nor S100B were associated with headaches in SLE patients. |
18. Papadaki et al. (2018) [26] | 76 SLE (37 primary NPSLE, 16 secondary NPSLE, 23 non-NPSLE) and 31 healthy controls | Not specified | Lower cerebral blood flow and volume in normal-appearing white matter areas in primary NPSLE patients | Primary NPSLE is characterized by significant hypoperfusion in cerebral white matter that appears normal on cMRI. The combination of DSC-MRI-measured blood flow in the brain semioval centre with conventional MRI may improve NPSLE diagnosis. |
19. Aloleimy et al. (2021) [4] | 57 SLE | - All headache: 54.4% - Migraine: 48.4% - TTH:35.5 | 25.8% with brain imaging abnormalities, white-matter hyperintensities most frequent | Musculoskeletal manifestations, positive anti-phospholipid (aPL) antibodies, and SLEDAI score ≥ 13.5 were identified as predictors of headache. |
20. Santos et al. (2021) [27] | 1,463 childhood-onset SLE patients | -All headache:52.2% | Not included | Headache, along with various neuropsychiatric syndromes, is common in childhood-onset SLE. |
21. Tian et al. (2023) [28] | 908 participants | Not specified | Not included | Meta-analysis suggesting a potential association between migraine and the risk of developing SLE. |
22. Our study | 179 SLE | -All headache:55% - TTH: 65% - Migraine: 27% | Brain MRI abnormalities were observed in 8% of headache sufferers, including venous sinus thrombosis (2%), ischemic stroke (5%) and white matter hyperintensities (1%). | Disease activity (SLEDAI) was significantly higher in the Headache Group. Muco-cutaneous manifestations were associated with tension-type and migraine headaches. APL antibody positivity showed a significant association with migraine and cluster headache. Neuropsychiatric manifestations, including ischemic stroke and venous sinus thrombosis, were more prevalent in the Headache Group, although not clinically significant. |