Cervicogenic headache (CH) is a secondary headache disorder arising from cervical structures and is frequently associated with pain, disability, and reduced quality of life. Botulinum toxin type A (BoNT-A) has been proposed as a therapeutic option due to its muscle-relaxing and antinociceptive properties; however, its efficacy in CH remains uncertain. This review aimed to evaluate the current evidence regarding the use of BoNT-A in the treatment of cervicogenic headache. A literature search was conducted in the PubMed/MEDLINE and Scopus databases, and studies assessing BoNT-A in adults with CH were included. Data on study characteristics, injection protocols, clinical outcomes, and adverse events were extracted and qualitatively synthesized. Five studies met the inclusion criteria, comprising four randomized controlled trials and one prospective study. Considerable heterogeneity was observed in diagnostic criteria, toxin formulations, injection techniques, targeted muscles, and outcome measures. Most studies reported reductions in headache intensity and frequency following BoNT-A treatment, particularly in trigger point-guided protocols and chronic or treatment-resistant populations. The trapezius and splenius capitis were the most frequently targeted muscles. Nevertheless, one high-quality placebo-controlled trial found no significant benefit over placebo. Overall, BoNT-A was well tolerated, with no serious adverse events reported. Although several studies suggest potential benefits of BoNT-A for cervicogenic headache, the current evidence remains inconclusive. Further well-designed studies using standardized diagnostic criteria and injection protocols are needed to better define its therapeutic role.
Background Heparanase (HPSE) uniquely cleaves heparan sulfate, the main component of the outer layer of endothelial cell plasma membranes, promoting tumour invasion and dissemination. However, it can also enhance tumour immune surveillance and clearance. HPSE’s versatility extends to pro-thrombotic properties, such as the promotion of tissue factor release. Interestingly, elevated HPSE levels have been found in ovarian cancer (OC), which has a notably high incidence of venous thrombosis. Previously, single-nucleotide polymorphisms (SNPs) of HPSE were shown to modulate mRNA and protein levels, possibly predicting disease outcomes. Methods and Results Given the potential role of HPSE in OC, the implications of three SNPs - rs11099592, rs4364254 and rs4693608 – were investigated on OC patients. In the discovery cohort, rs11099592 TT genotype and rs4364254 C allele carriers showed lower survival time than their counterparts (log-rank test, p = 0.025 and p = 0.001, respectively). Validation cohort analysis confirmed the worse prognosis associated with the rs11099592 T allele and rs4364254 C allele in non-serous (log-rank test, p = 0.016) and platinum-resistant (log-rank test, p = 0.044) OC patients, respectively. The rs4364254 C allele was associated with reduced HPSE expression in peripheral blood components (PBCs; χ 2 , p = 0.005), suggesting a protective role for HPSE in OC patients. Conclusions HPSE rs11099592 and rs4364254 showed prognostic value, with T and C allele carriers, respectively, displaying worse clinical outcomes. These results indicate that HPSE could enable a tumour microenvironment shift towards a less aggressive cancer behaviour, facilitating leukocyte migration and anti-tumour responses. Further research should explore the dual mechanisms of this protein to improve OC management.
Background: Spondyloarthritis (SpA) comprise a complex group of inflammatory arthropathies that can involve both axial and peripheral joints, often associated with extra-musculoskeletal manifestations, particularly psoriasis. The distinction between Psoriatic Arthritis (PsA) with axial involvement and axial SpA (axSpA) with concomitant psoriasis has been a topic of debate, potentially influencing clinical decisions. Objectives: To identify clinical and demographic characteristics associated with clinician's decision to diagnose patients with psoriasis and axial disease as axSpA or as PsA with axial involvement in practical clinical settings. Methods: All adult patients registered in the Rheumatic Portuguese Disease Register (Reuma.pt) with the clinical diagnosis of PsA with axial involvement (axPsA) or axSpA with concomitant psoriasis were included. Bivariate and multivariate analysis were performed to identify clinical and demographic characteristics associated with the clinical diagnosis of axPsA or axSpA. Results: Out of 854 patients, 88.3% (n=754) received a diagnosis of axPsA and 11.7% (n=100) were diagnosed with axSpA with psoriasis. The diagnosis of axPsA included concomitant peripheral involvement in 82.2% of patients (n=620) and exclusive axial involvement in 17.8% (n=134). In axSpA diagnosis, the prevalence of concomitant peripheral involvement was 48% (n=48). Considering the whole cohort, axSpA diagnosis was associated with less peripheral involvement (OR 0.20, 95% CI 0.13-0.31; p<0.001), younger age at diagnosis (axSpA 36.7 ± 9.4 vs axPsA 43.8 ± 13.1; p<0.001) and at symptom onset (axSpA 30.1 ± 9.7 vs axPsA 39.6 ± 12.9; p<0.001) and higher positivity for HLA-B27 (OR 8.95; 95% CI 5.24-15.28; p<0.001) (Table 1). Regarding extra-articular manifestations, uveitis (OR 7.59; 95% CI 4.5-12.81; p<0.001) and inflammatory bowel disease (OR 21.02; 95% CI 8.01-55.18; p<0.001) were associated positively, while dactylitis was associated negatively with axSpA diagnosis (OR 0.13; 95% CI 0.06-0.29; p<0.001). axSpA patients more commonly received bDMARDs (OR 3.82; 2.13-6.84; p<0.001) and had a longer time from symptom onset until start of first bDMARD (axSpA 13.7 ± 9.3 vs axPsA 9.5 ± 9.1; p<0.001). Cardiovascular comorbidities were negatively associated with axSpA (OR 0.53; 95% CI 0.32 - 0.88; p<0.013). Multivariate analysis identified HLA-B27 positivity, younger age at symptom onset, presence of uveitis and inflammatory bowel disease and lower prevalence of dactylitis as independently associated with axSpA diagnosis. When considering patients with exclusive axial involvement (N=186), axSpA diagnosis was associated with a younger age at diagnosis (axSpA 36.4 ± 10.3; vs axPsA 43.9 ± 13.8; p<0.001) and at symptom onset (axSpA 29.3± 10.1 vs axPsA 38.3 ± 13.6; p<0.001), a higher prevalence of HLA-B27 (OR 8.55; 95% CI 3.59-20.4; p<0.001) and uveitis (OR 7.7; 95% CI 3.0-19.2; p<0.001) (Table 2). Regarding treatment, axSpA patients were more frequently treated with bDMARDs (OR 4.59; 95% CI 2.13 - 9.90; p<0.001) and had a longer time from symptom onset until start of first bDMARD (axSpA 14.8 ± 10.2 vs axPsA 8.5 ± 7.9; p<0.001). However, multivariate analysis did not identify any variables independently associated with the diagnosis of axPsA or axSpA. Conclusion: Patients with axPsA diagnosis exhibit more frequently concomitant peripheral involvement, whereas those with axSpA diagnosis have more often exclusive axial involvement, are younger and more frequently HLA-B27 positive. However, when considering patients with exclusive axial involvement, no differences could be identified between axSpA with psoriasis and axPsA diagnosis. In clinical practice, clinicians tend to diagnose patients with psoriasis as axSpA when axial involvement predominates and there are no peripheral manifestations. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.
We report the case of a 56-year-old woman who presented to the Emergency Department with unilateral exophthalmos of the left eye, accompanied by recurrent bitemporal headache. Her past medical history was significant for hypertension, ischemic heart disease, anxiety, depression, and obesity. On clinical examination, the patient was hemodynamically stable, alert, and fully oriented. A brief neurological assessment revealed no focal deficits. Initial laboratory investigations, including complete blood count, serum electrolytes, and coagulation profile, were within normal limits. D-dimer levels were negative. A contrast-enhanced cranial computed tomography (CT) scan ruled out both intracranial space-occupying lesions and cerebral venous sinus thrombosis. Orbital magnetic resonance imaging (MRI) excluded any primary orbital pathology. Endocrine evaluation of the hypothalamic-pituitary-thyroid axis revealed a suppressed thyroid-stimulating hormone (TSH) level of 0.010 mUI/L (reference range: 0.27-4.20 mUI/L) and a free T4 level of 21.59 pmol/L (reference range, adjusted for age and sex: 8.24-21.0 pmol/L). Given the suspicion of Graves-Basedow disease with atypical unilateral ocular involvement, an autoimmune panel was performed. TSH receptor antibodies (TRAb) were markedly elevated at 11.0 U/L (reference range: 0-1.8 U/L), confirming the diagnosis of Graves' disease. Graves' disease is an autoimmune thyroid disorder that typically presents with bilateral exophthalmos due to inflammatory changes and expansion of the extraocular muscles and orbital adipose tissue. However, unilateral exophthalmos, although uncommon, can occur as a manifestation of Graves' orbitopathy.
