Idiopathic intracranial hypertension, polycystic-ovary syndrome, and thrombophilia

Document Type

Article

Abstract

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.

Medical Subject Headings

Adolescent; Adult; Blood Coagulation Tests; Estrogens (blood); Female; Fibrinolysis; Humans; Magnetic Resonance Imaging; Methylenetetrahydrofolate Reductase (NADPH2) (genetics); Middle Aged; Obesity (complications, diagnosis); Polycystic Ovary Syndrome (complications, diagnosis, genetics); Pregnancy; Pseudotumor Cerebri (diagnosis, etiology, genetics); Thrombophilia (complications, diagnosis, genetics)

Publication Date

2-1-2005

Publication Title

The Journal of laboratory and clinical medicine

ISSN

0022-2143

Volume

145

Issue

2

First Page

72

Last Page

82

PubMed ID

15746649

Digital Object Identifier (DOI)

10.1016/j.lab.2004.09.011

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