Idiopathic intracranial hypertension, polycystic-ovary syndrome, and thrombophilia

doi:10.1016/j.lab.2004.09.011

Journal of Laboratory and Clinical Medicine

Volume 145, Issue 2, February 2005, Pages 72-82

https://doi.org/10.1016/j.lab.2004.09.011 Get rights and content

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 ≥ 30 to < 40), and 19 (51%) were extremely obese (BMI ≥ 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 (≥ 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.

Section snippets

Cases

The Jewish Hospital Institutional Review Board approved this consecutive-case study. Written informed consent was obtained from all subjects, and the study was carried out in accordance with the ethical standards for human experimentation established by the Declaration of Helsinki of 1975 and revised in 1983. Sixty-five women with well-defined IIH (Appendix I) were studied after they were found to have met the following 5 diagnostic criteria1, 2, 3, 4, 5, 6: increased intracranial pressure,

Controls

By selection, the 30 white adult women used as serologic controls did not differ from the IIH patients with regard to race or age (Table II). When compared with that of the 65 IIH cases, the distribution of BMI in the 30 adult white serologic controls was shifted away from the obese and extreme-obesity categories (P = .01); Table II.⁴⁰

Cases

All 65 IIH patients underwent magnetic-resonance imaging and magnetic resonance venograms at the time of study entry; only 1 patient (case 16, Appendix I) had

Discussion

In part because the known causes of IIH vary10, 11, 15, 16, 29, 30, 31, 32, 33, 41, 42 and it is surmised that other unknown factors also cause the disorder,1, 2, 3, 4, 5, 6, 7, 8 information on which medical and surgical therapies are truly beneficial and which are potentially harmful is inadequate.⁸ Better understanding of IIH’s origins15, 16 should advance novel medical therapies for IIH. Congruent with our original report,¹⁵ in the study reported here we have linked IIH with

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