DISCUSSION:
The incidence of CSVT is estimated to be 0.22 to 1.57 per 100,000, with a more observed propensity in females compared to males of a ratio of 3:1, with 70-80% of cases are female in their childbearing age. This disproportion could be explained by one of the proposed mechanisms of CSVT, attributed to the hypercoagulable state, which is common in pregnancy, puerperium, and combined oral contraceptive use.2
Many proposed pathophysiological mechanisms could explain CSVT, with at least two projected. First, thrombosis of cerebral veins or dural sinus impeding blood drainage leading to parenchymal insult and disruption of the blood-brain barrier, secondary to build up of venous and capillary pressure that impairs cerebral blood flow.3 Secondly, non-resolved venous thrombus impairing cerebrospinal fluid (CSF) absorption via arachnoid granulation and increase intracranial pressure, leading to cytotoxic and vasogenic edema and eventually may cause parenchymal hemorrhage. 3 These mechanisms are demonstrated on neuroimaging such as MRI methods, diffusion-weighted MRI, and perfusion-weighted MRI showing cytotoxic and vasogenic edema .3
The etiology and predisposing risk factors of CSVT are several, with Virchow triad, associated with blood stasis, hypercoagulability, and alteration in the vessel wall, being the center of its pathophysiology\sout, For instance, inherited or acquired thrombophilia, Para-meningeal infection, trauma, and neurosurgical procedures, medications, and many inflammatory diseases could attribute as causative factors of CSVT that may exist alone or in a bundle with a synergistic effect. For example, combined oral contraceptive (COC) with co-existing mild to severe inherited thrombophilia such as factor prothrombin gene mutation increases the odds of CSVT. Mutated Factor V Leiden (R506Q) and MTHFR C677T are the most common genetically predisposed thrombophilia, accounting for 10% and 9.3%, respectively, of venous thromboembolism. 4 Factor VIII is a main propagating factor in the coagulation cascade has been attributed to the thrombotic state. One study that looked at elevated serum factor VIII and risk of recurrence of venous showed, serum levels greater than 150 mcg/L are associated with a 5-fold risk for venous thrombosis. 4
In a systematic review and meta-analysis on COC, thrombophilia and the risk of venous thromboembolism, demonstrated; risk of VTE in COC users with mild to severe thrombophilia is 6-fold higher with a rate ratio [RR], 5.89; 95% confidence interval [CI], 4.21–8.23) and 7-fold (RR, 7.15; 95% CI, 2.93–17.45), respectively. Cochrane reviews noted that the use of combined oral contraceptives increased the risk of venous thrombosis (relative risk (RR) 3.5, 95% confidence interval (CI) 2.9 to 4.3). as well as arterial thrombosis (RR1.7, 95% CI 1.5 to 1.9) compared with non‐use 5
Interestingly enough, Factor VIII is a propagating factor in both intrinsic and extrinsic coagulation pathways, which is stabilized by the von Willebrand factor complex (vWF). 6 Although its level can be high in as acute phase response in the setting of acute strokes, in a study by O’Donnell et al., half of their patients showed elevated Factor VIII that could be attributed to vWF, which supports the notion that elevated factor VIII remains the driving force behind thrombotic events. 6
Factor VIII relevance in prothrombic syndrome was first recognized in 1990, where hemophiliac patients with factor VIII deficiency had a protective effect against coronary heart diseases. 7Over the past few years, compelling evidence showed the risk of arterial thrombosis in patients for elevated serum Factor VIII. Folsom et al. conducted a prospective study on over 15,000 patients without cardiovascular risk factors, reported 191 ischemic strokes events that had Factor VIII in the uppermost quartile showed an adjusted relative risk factor of 1.93. 8
Our patient presented with a rare combination of veno-arterial disease (ischemic stroke with CSVT), which had elevated factor VIII of 231.7 and 243.5% provoked by OCP use. Previously, CSVT has been linked with the use of oral contraceptives, with its risk being higher in genetically predisposed patients with underlying thrombophilia. Furthermore, OCP is considered a risk factor for ischemic stroke. According to the WHO, the odds ratio for ischemic stroke in women who take oral contraceptives is 2.99 (1.65 to 5.40). 1
However, our case differs from those reported in the literature in that the patient suffered from concomitant CSVT and ischemic stroke (specifically PICA distribution). Her presentation resulted from 1.6-fold higher serum Factor VIII provoking a thrombotic state in the setting of oral contraceptive use. In addition, our patient presented with headache and nausea and was found to have cerebellar signs, and she had quick recovery clinically and radiologically.