We studied
thrombophilia, hypofibrinolysis, and
polycystic-ovary syndrome (PCOS) in 65 women consecutively referred because of
idiopathic intracranial hypertension (IIH) as a means of better understanding the origin of IIH, with the ultimate goal of developing novel medical
therapies for IIH. Our hypothesis: IIH results in part from inadequate drainage of cerebrospinal fluid (CSF) resulting from thrombotic obstruction to CSF resorption-outflow, favored by
thrombophilia-hypofibrinolysis. We conducted the polymerase chain reaction (PCR) and assessed serologic coagulation measures in 65 women (64 of them white) with IIH, PCR in 102 healthy white female controls (72 children, 30 age-matched adults), and serologic measures in the 30 adults. Of the 65 patients, 37 (57%) were found to have PCOS; 16 (43%) were obese (BMI > or = 30 to < 40), and 19 (51%) were extremely obese (BMI > or = 40). Of the 65 women with IIH, 25 (38%) were homozygous for the thrombophilic C677T MTHFR mutation, compared with 14% of controls (14/102) ( P = .0002). Thrombophilic high concentrations of
factor VIII (>150%) were present in 9 of 65 (14%) IIH cases, compared with 0 of 30 controls (0%) (Fisher's p [p f ] = .053). An increased concentration of
lipoprotein A (> or = 35 mg/dL), associated with hypofibrinolysis, was present in 19 of 65 IIH cases (29%), compared with 3 of 30 controls (10%) (p f = .039). IIH occurred in 18 of 65 IIH patients taking
estrogen-
progestin contraceptives (28%), in 6 patients taking
hormone-replacement therapy (9%), and in 5 pregnant subjects (8%). We speculate that PCOS, associated with
obesity and extreme
obesity, is a treatable promoter of IIH. We also speculate that if
thrombophilia-hypofibrinolysis and subsequent
thrombosis are associated with reduced CSF resorption in the arachnoid villi of the brain,
thrombophilia and hypofibrinolysis-often exacerbated by thrombophilic exogenous
estrogens, pregnancy, or the paradoxical hyperestrogenemia of PCOS-are treatable promoters of IIH.