In recent years, CVT has attracted more attention to the morbidity increasing . It presents various neurological signs and symptoms, and its common clinical presentations (e.g., headache, seizures, focal neurological deficits, altered consciousness, and papilledema) can present in isolation or association with other symptoms . Headache, the most common symptom in CVT, was present in nearly 90% of patients in the International Study on Cerebral Vein and Dural Sinus Thrombosis . Similar headache frequency was reported in our study and 37.8% CVT patients presented isolated headache (Table 1). For this reason, patients with primary headaches were selected as the control group.
Due to complex and nonspecific clinical findings of CVT, delay in diagnosis and misdiagnosis frequently occurred. It’s reported that an initial misdiagnosis of CVT could occur in 73% of patients  and delays in diagnosis for over 10 days could happen in 40% of patients admitted to the hospital . A median delay of 7 days (mean ± SD, 18.3 ± 59.4 days) was reported . Even though they received standard anticoagulation, the deterioration of neurological function was hard to be reversed or stopped . Over 50% of the discharged patients complained about headache and 20–30% complained about depression, concentration problems, linguistic difficulties, or cognitive impairment, which had an impact on their psychosocial functioning and employment status [26–28]. Therefore, finding an accurate and accessible indicator to achieve prompt diagnosis is essential and important since it might reduce the incidence of death and long-term sequelae .
Up to now, D-dimer is the only recognized blood index related to CVT. However, there are some shortages. First, it was considered to help excluding CVT for its low positive predictive value . Second, CVT patients with less clot burden may be particularly at risk of false-negative results . Furthermore, a number of different D-dimer assays are available with variable test performance characteristics . Therefore, it is expected to access a better index from routine blood work.
A close link between inflammation and thrombosis has been detected in previous studies [31, 32]. Although the pathophysiology of CVT has not been defined yet, the evidence is currently accumulating for the role of inflammation in CVT. Gu et al.  have demonstrated that recombinant human soluble thrombomodulin reduced infarct volume in a model of CVT, via inhibiting inflammation by blocking high mobility group box 1 (HMGB1) binding to a receptor for advanced glycation end-products. Rashad and Nagai et al. [6, 33] found intense inflammatory cell infiltration on the infarct area and high level in several inflammation indicators in the early stage of CVT. Also, previous clinical studies have found inflammation indicators (e.g., MPV, RDW, CRP, ESR, and bilirubin) increasing in patients with CVT [8, 34, 35], potently hinting the correlation between inflammation and the severity and outcome of CVT. Consistent with the previous results, the high levels of WBC, monocyte, neutrophils, and platelets were found in CVT patients compared with the control group. Incompatibly, the MPV value was found within the normal range with a lower value in the CVT group. Several studies believed that MPV is not able to reflect inflammation properly, and that could decrease in the acute stage . Based on the results of this study, it is hard to define whether a lower MPV level resulted from a low number of participants or the pathophysiological properties of CVT. All of these pathologic processes, well-known risk factors, and laboratory findings of CVT were associated with an inflammatory state. Regardless of the direction of the relationship, it was believed to have a significant correlation between inflammation and CVT.
With the growing understanding of inflammation, NLR, PLR, SII, and MHR have been widely investigated in malignancies, inflammatory diseases, cardiovascular and cerebrovascular diseases. These indicators are more stable than individual blood parameters, which may be altered by several variables (e.g., dehydration, overhydration, and blood specimen handling) . Indicating the balance of the neutrophils (the active component of the inflammation) with the lymphocytes (the regulatory and protective component), NLR was found to be a good prognostic factor in functional outcomes and mortality in patients with severe traumatic brain injury . Zeng et al.  demonstrated that both NLR and PLR can be used to predict the diagnosis and prognosis of nasopharyngeal carcinoma . Many studies revealed that DVT improves the levels of NLR and PLR [11, 39]. As for SII, considering together neutrophil, platelet, and lymphocyte, it suggested the balance between host systemic inflammation and coagulation status comprehensively, thus it was used in predicting outcomes of malignancies and ischemic stroke [15–17, 40, 41]. Monocytes were reported to involve in inflammatory and pro-thrombotic pathways, while HDL interferes with the pro-inflammatory effects of monocytes by inhibiting the migration of macrophages [42–45]. Therefore, it assumed that MHR was a reliable and more comprehensive indicator of inflammation. Indeed, it has been reported that higher MHR was associated with poor outcome of cardiovascular diseases and renal dysfunction [18, 19, 45]. For this reason, we hypothesized the association between SII, NLR, PLR, and MHR with the onset of CVT. Our study confirmed that the levels of NLR, PLR, SII, and MHR were significantly higher in CVT patients. ROC curves were analyzed and showed a satisfying result. The area under the ROC curve (AUC) of NLR, PLR, SII, and MHR was 0.826, 0.702, 0.827, and 0.657, respectively, suggesting the power of SII, NLR, and PLR in predicting CVT. NLR and SII yielded a sensitivity of 0.780 and 0.844 and a specificity of 0.800 and 0.750, respectively. Basing on the multivariable regression analysis, the degrees of SII and MHR remained as independent indicators of CVT that the AUC was 0.847 representing a good predicting power. Therefore, NLR, PLR, SII, and MHR could help clinicians to suspect CVT, especially among the patients with unexplained headache and a normal plain CT, then decide which patients require MRI/MRV immediately for confirmation of the diagnosis. These would help to shorten the time from the onset of symptoms to diagnosis and reduce misdiagnosis.
Moreover, the results of this study found that the levels of SII, NLR, and PLR were positively correlated with the baseline NHISS degree, indicating the vital role of inflammation in the progression of CVT. However, there was no difference in inflammation indicators among patients with different numbers of cerebral venous sinus involved. In another word, SII, NLR, and PLR levels were not correlated with the anatomic extent of thrombosed sinuses, which enable them to better identify patients with lighting clot burden than D-dimer .
Furthermore, the NLR and SII levels were distinctly higher in the acute-subacute stage of CVT, which was consistent with the results of another study . Wang et al.  demonstrated that inflammation may develop soon after CVT and gradually decrease during the course. Inflammation may affect mainly during the early stage. The previous study on DVT mouse model found that neutropenic mice developed no or significantly smaller thrombi compared with controls , but it needed further research to confirm whether an early intervention of inflammation is benefited for CVT patients.
The results of this study focused on the differences between CVT patients and primary headache patients, which might help more in clinical practice since CVT patients presenting isolated headache were more likely to be at risk of delay in diagnosis and misdiagnosis. However, there were still some limitations. First, there was not enough study population because of the low morbidity of CVT. Second, as a retrospective study, there was some missing data and only baseline values were analyzed rather than the temporal trend. Third, it cannot explain whether the milieu of increased inflammation was present before the onset of disease and caused the thrombus or it was a response to the thrombus.